Abstract
Cancer remains a leading cause of death in the United States and other developed countries. In nearly all cases, the cause of death is related to complications associated with tumor metastasis to distant sites such as the brain, lung, liver, and bone. A central feature of tumor progression is the acquisition of a blood supply, which provides nutrients for the growing tumor as well as conduits for transport of cancer cells. Our understanding of how a tumor acquires and manipulates a blood supply has been gleaned largely from animal models, but more recent advances in tissue engineering and microfabrication have led to clever 3D in vitro models of tumors that include blood vessels. This chapter will first briefly review the process of blood vessel growth including our knowledge of blood vessels within the cancer microenvironment, and discuss the most recent advances to mimic blood vessel growth in the tumor microenvironment using 3D in vitro culture methods. Finally, we discuss several important factors that control blood vessel growth including hypoxia, cellular metabolism, and tissue mechanics, which provide rich opportunities for future investigation.
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References
Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186
Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407(6801):249–257. doi:10.1038/35025220
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:10.1016/j.cell.2011.02.013
Semenza GL (2012) Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci 33(4):207–214. doi:10.1016/j.tips.2012.01.005
Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med 324(1):1–8. doi:10.1056/NEJM199101033240101
Morton CL, Houghton PJ (2007) Establishment of human tumor xenografts in immunodeficient mice. Nat Protoc 2(2):247–250. doi:10.1038/nprot.2007.25
Richmond A, Su Y (2008) Mouse xenograft models vs GEM models for human cancer therapeutics. Dis Model Mech 1(2–3):78–82. doi:10.1242/dmm.000976
Dalen H, Burki HJ (1971) Some observations on the three-dimensional growth of L5178Y cell colonies in soft agar culture. Exp Cell Res 65(2):433–438
Ehsan SM, Welch-Reardon KM, Waterman ML, Hughes CCW, George SC (2014) A three-dimensional in vitro model of tumor cell intravasation. Integr Biol (UK) 6(6):603–610. doi:10.1039/c3ib40170g
Carver K, Ming X, Juliano RL (2014) Multicellular tumor spheroids as a model for assessing delivery of oligonucleotides in three dimensions. Mol Ther Nucl Acids 3. doi:ARTN e153 10.1038/mtna.2014.5
Vakoc BJ, Lanning RM, Tyrrell JA, Padera TP, Bartlett LA, Stylianopoulos T, Munn LL, Tearney GJ, Fukumura D, Jain RK, Bouma BE (2009) Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nat Med 15(10):1219–U1151. doi:10.1038/nm.1971
Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3(6):401–410. doi:10.1038/nrc1093
Fernandez-Sanchez ME, Barbier S, Whitehead J, Bealle G, Michel A, Latorre-Ossa H, Rey C, Fouassier L, Claperon A, Brulle L, Girard E, Servant N, Rio-Frio T, Marie H, Lesieur S, Housset C, Gennisson JL, Tanter M, Menager C, Fre S, Robine S, Farge E (2015) Mechanical induction of the tumorigenic beta-catenin pathway by tumour growth pressure. Nature 523(7558):92–95. doi:10.1038/nature14329
Ou G, Weaver VM (2015) Tumor-induced solid stress activates beta-catenin signaling to drive malignant behavior in normal, tumor-adjacent cells. BioEssays 37(12):1293–1297. doi:10.1002/bies.201500090
Augustin HG, Koh GY, Thurston G, Alitalo K (2009) Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 10(3):165–177. doi:10.1038/nrm2639
Saharinen P, Eklund L, Miettinen J, Wirkkala R, Anisimov A, Winderlich M, Nottebaum A, Vestweber D, Deutsch U, Koh GY, Olsen BR, Alitalo K (2008) Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. Nat Cell Biol 10(5):527–537. doi:10.1038/ncb1715
Cascone T, Heymach JV (2012) Targeting the angiopoietin/Tie2 pathway: cutting tumor vessels with a double-edged sword? J Clin Oncol (Official Journal of the American Society of Clinical Oncology) 30(4):441–444. doi:10.1200/jco.2011.38.7621
Radu M, Semenova G, Kosoff R, Chernoff J (2014) PAK signalling during the development and progression of cancer. Nat Rev Cancer 14(1):13–25
Fryer BH, Field J (2005) Rho, Rac, Pak and angiogenesis: old roles and newly identified responsibilities in endothelial cells. Cancer Lett 229(1):13–23. doi:http://dx.doi.org/10.1016/j.canlet.2004.12.009
Ghosh K, Thodeti CK, Dudley AC, Mammoto A, Klagsbrun M, Ingber DE (2008) Tumor-derived endothelial cells exhibit aberrant Rho-mediated mechanosensing and abnormal angiogenesis in vitro. Proc Natl Acad Sci U S A 105(32):11305–11310. doi:10.1073/pnas.0800835105
Halder G, Dupont S, Piccolo S (2012) Transduction of mechanical and cytoskeletal cues by YAP and TAZ. Nat Rev Mol Cell Biol 13(9):591–600
Dupont S (2016) Role of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction. Exp Cell Res. doi:http://dx.doi.org/10.1016/j.yexcr.2015.10.034
Piccolo S, Cordenonsi M, Dupont S (2013) Molecular pathways: YAP and TAZ take center stage in organ growth and tumorigenesis. Clin Cancer Res (An Official Journal of the American Association for Cancer Research) 19(18):4925–4930. doi:10.1158/1078-0432.ccr-12-3172
Nakatsu MN, Hughes CCW (2008) An optimized three-dimensional in vitro model for the analysis of angiogenesis. Angiogenesis: in vitro systems. Methods Enzymol 443:65. doi:10.1016/S0076-6879(08)02004-1
Welch-Reardon KM, Ehsan SM, Wang KH, Wu N, Newman AC, Romero-Lopez M, Fong AH, George SC, Edwards RA, Hughes CCW (2014) Angiogenic sprouting is regulated by endothelial cell expression of Slug. J Cell Sci 127(9):2017–2028. doi:10.1242/jcs.143420
Kim J, Chung M, Kim S, Jo DH, Kim JH, Jeon NL (2015) Engineering of a biomimetic pericyte-covered 3D microvascular network. PLoS One 10(7):e0133880. doi:10.1371/journal.pone.0133880
Zheng Y, Chen J, Craven M, Choi NW, Totorica S, Diaz-Santana A, Kermani P, Hempstead B, Fischbach-Teschl C, Lopez JA, Stroock AD (2012) In vitro microvessels for the study of angiogenesis and thrombosis. Proc Natl Acad Sci U S A 109(24):9342–9347. doi:10.1073/pnas.1201240109
Jeon JS, Bersini S, Whisler JA, Chen MB, Dubini G, Charest JL, Moretti M, Kamm RD (2014) Generation of 3D functional microvascular networks with human mesenchymal stem cells in microfluidic systems. Integr Biol-Uk 6(5):555–563. doi:10.1039/c3ib40267c
Moya ML, Hsu YH, Lee AP, Hughes CC, George SC (2013) In vitro perfused human capillary networks. Tissue Eng Part C Methods 19(9):730–737. doi:10.1089/ten.TEC.2012.0430
Song JW, Munn LL (2011) Fluid forces control endothelial sprouting. Proc Natl Acad Sci U S A 108(37):15342–15347. doi:10.1073/pnas.1105316108
Nguyen DH, Stapleton SC, Yang MT, Cha SS, Choi CK, Galie PA, Chen CS (2013) Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro. Proc Natl Acad Sci U S A 110(17):6712–6717. doi:10.1073/pnas.1221526110
Bischel LL, Young EW, Mader BR, Beebe DJ (2013) Tubeless microfluidic angiogenesis assay with three-dimensional endothelial-lined microvessels. Biomaterials 34(5):1471–1477. doi:10.1016/j.biomaterials.2012.11.005
Newman AC, Chou W, Welch-Reardon KM, Fong AH, Popson SA, Phan DT, Sandoval DR, Nguyen DP, Gershon PD, Hughes CC (2013) Analysis of stromal cell secretomes reveals a critical role for stromal cell-derived hepatocyte growth factor and fibronectin in angiogenesis. Arterioscler Thromb Vasc Biol 33(3):513–522. doi:10.1161/ATVBAHA.112.300782
Newman AC, Nakatsu MN, Chou W, Gershon PD, Hughes CC (2011) The requirement for fibroblasts in angiogenesis: fibroblast-derived matrix proteins are essential for endothelial cell lumen formation. Mol Biol Cell 22(20):3791–3800. doi:10.1091/mbc.E11-05-0393
Wang XL, Phan DTT, Sobrino A, George SC, Hughes CCW, Lee AP (2016) Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels. Lab Chip 16(2):282–290. doi:10.1039/c5lc01050k
Chen X, Aledia AS, Ghajar CM, Griffith CK, Putnam AJ, Hughes CC, George SC (2009) Prevascularization of a fibrin-based tissue construct accelerates the formation of functional anastomosis with host vasculature. Tissue Eng Part A 15(6):1363–1371. doi:10.1089/ten.tea.2008.0314
Chen X, Aledia AS, Popson SA, Him L, Hughes CC, George SC (2010) Rapid anastomosis of endothelial progenitor cell-derived vessels with host vasculature is promoted by a high density of cotransplanted fibroblasts. Tissue Eng Part A 16(2):585–594. doi:10.1089/ten.TEA.2009.0491
Alonzo LF, Moya ML, Shirure VS, George SC (2015) Microfluidic device to control interstitial flow-mediated homotypic and heterotypic cellular communication. Lab Chip 15(17):3521–3529. doi:10.1039/c5lc00507h
Gilkes DM, Semenza GL, Wirtz D (2014) Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat Rev Cancer 14(6):430–439. doi:10.1038/nrc3726
Harris AL (2002) Hypoxia–a key regulatory factor in tumour growth. Nat Rev Cancer 2(1):38–47. doi:10.1038/nrc704
Vaupel P, Mayer A, Hockel M (2004) Tumor hypoxia and malignant progression. Methods Enzymol 381:335–354. doi:10.1016/S0076-6879(04)81023-1
Baudino TA, McKay C, Pendeville-Samain H, Nilsson JA, Maclean KH, White EL, Davis AC, Ihle JN, Cleveland JL (2002) c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression. Genes Dev 16(19):2530–2543. doi:10.1101/gad.1024602
Grimes DR, Kelly C, Bloch K, Partridge M (2014) A method for estimating the oxygen consumption rate in multicellular tumour spheroids. J R Soc Interface 11(92):20131124. doi:10.1098/rsif.2013.1124
Adams JM, Difazio LT, Rolandelli RH, Lujan JJ, Hasko G, Csoka B, Selmeczy Z, Nemeth ZH (2009) HIF-1: a key mediator in hypoxia. Acta Physiol Hung 96(1):19–28. doi:10.1556/APhysiol.96.2009.1.2
Semenza GL (2007) Hypoxia-inducible factor 1 (HIF-1) pathway. Science’s STKE: signal transduction knowledge environment 2007 (407):cm8. doi:10.1126/stke.4072007cm8
Ke Q, Costa M (2006) Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol 70(5):1469–1480. doi:10.1124/mol.106.027029
Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9(6):653–660. doi:10.1038/nm0603-653
Zhou W, Dosey TL, Biechele T, Moon RT, Horwitz MS, Ruohola-Baker H (2011) Assessment of hypoxia inducible factor levels in cancer cell lines upon hypoxic induction using a novel reporter construct. PLoS One 6(11):e27460. doi:10.1371/journal.pone.0027460
Krock BL, Skuli N, Simon MC (2011) Hypoxia-induced angiogenesis: good and evil. Genes Cancer 2(12):1117–1133. doi:10.1177/1947601911423654
Byrne MB, Leslie MT, Gaskins HR, Kenis PJ (2014) Methods to study the tumor microenvironment under controlled oxygen conditions. Trends Biotechnol 32(11):556–563. doi:10.1016/j.tibtech.2014.09.006
Piret JP, Mottet D, Raes M, Michiels C (2002) CoCl2, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in hepatoma cell line HepG2. Ann N Y Acad Sci 973:443–447
Brennan MD, Rexius-Hall ML, Elgass LJ, Eddington DT (2014) Oxygen control with microfluidics. Lab Chip 14(22):4305–4318. doi:10.1039/c4lc00853g
Funamoto K, Zervantonakis IK, Liu Y, Ochs CJ, Kim C, Kamm RD (2012) A novel microfluidic platform for high-resolution imaging of a three-dimensional cell culture under a controlled hypoxic environment. Lab Chip 12(22):4855–4863. doi:10.1039/c2lc40306d
Wang L, Liu W, Wang Y, Wang JC, Tu Q, Liu R, Wang J (2013) Construction of oxygen and chemical concentration gradients in a single microfluidic device for studying tumor cell-drug interactions in a dynamic hypoxia microenvironment. Lab Chip 13(4):695–705. doi:10.1039/c2lc40661f
Ochs CJ, Kasuya J, Pavesi A, Kamm RD (2014) Oxygen levels in thermoplastic microfluidic devices during cell culture. Lab Chip 14(3):459–462. doi:10.1039/c3lc51160j
Clark LC Jr, Lyons C (1962) Electrode systems for continuous monitoring in cardiovascular surgery. Ann N Y Acad Sci 102:29–45
Esipova TV, Karagodov A, Miller J, Wilson DF, Busch TM, Vinogradov SA (2011) Two new “protected” oxyphors for biological oximetry: properties and application in tumor imaging. Anal Chem 83(22):8756–8765. doi:10.1021/ac2022234
Griffith CK, Miller C, Sainson RC, Calvert JW, Jeon NL, Hughes CC, George SC (2005) Diffusion limits of an in vitro thick prevascularized tissue. Tissue Eng 11(1–2):257–266. doi:10.1089/ten.2005.11.257
De Bock K, Georgiadou M, Carmeliet P (2013) Role of endothelial cell metabolism in vessel sprouting. Cell Metab 18(5):634–647. doi:10.1016/j.cmet.2013.08.001
De Bock K, Georgiadou M, Schoors S, Kuchnio A, Wong BW, Cantelmo AR, Quaegebeur A, Ghesquiere B, Cauwenberghs S, Eelen G, Phng LK, Betz I, Tembuyser B, Brepoels K, Welti J, Geudens I, Segura I, Cruys B, Bifari F, Decimo I, Blanco R, Wyns S, Vangindertael J, Rocha S, Collins RT, Munck S, Daelemans D, Imamura H, Devlieger R, Rider M, Van Veldhoven PP, Schuit F, Bartrons R, Hofkens J, Fraisl P, Telang S, Deberardinis RJ, Schoonjans L, Vinckier S, Chesney J, Gerhardt H, Dewerchin M, Carmeliet P (2013) Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154(3):651–663. doi:10.1016/j.cell.2013.06.037
Verdegem D, Moens S, Stapor P, Carmeliet P (2014) Endothelial cell metabolism: parallels and divergences with cancer cell metabolism. Cancer Metab 2:19. doi:10.1186/2049-3002-2-19
Wenzel C, Riefke B, Grundemann S, Krebs A, Christian S, Prinz F, Osterland M, Golfier S, Rase S, Ansari N, Esner M, Bickle M, Pampaloni F, Mattheyer C, Stelzer EH, Parczyk K, Prechtl S, Steigemann P (2014) 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions. Exp Cell Res 323(1):131–143. doi:10.1016/j.yexcr.2014.01.017
Wright BK, Andrews LM, Jones MR, Stringari C, Digman MA, Gratton E (2012) Phasor-FLIM analysis of NADH distribution and localization in the nucleus of live progenitor myoblast cells. Microsc Res Tech 75(12):1717–1722. doi:10.1002/jemt.22121
Wright BK, Andrews LM, Markham J, Jones MR, Stringari C, Digman MA, Gratton E (2012) NADH distribution in live progenitor stem cells by phasor-fluorescence lifetime image microscopy. Biophys J 103(1):L7–L9. doi:10.1016/j.bpj.2012.05.038
Walsh AJ, Cook RS, Sanders ME, Aurisicchio L, Ciliberto G, Arteaga CL, Skala MC (2014) Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer. Cancer Res 74(18):5184–5194. doi:10.1158/0008-5472.CAN-14-0663
Walsh AJ, Castellanos JA, Nagathihalli NS, Merchant NB, Skala MC (2015) Optical imaging of drug-induced metabolism changes in murine and human pancreatic cancer organoids reveals heterogeneous drug response. Pancreas. doi:10.1097/MPA.0000000000000543
Okkelman IA, Dmitriev RI, Foley T, Papkovsky DB (2016) Use of Fluorescence Lifetime Imaging Microscopy (FLIM) as a timer of cell cycle S phase. PLoS One 11(12):e0167385. doi:10.1371/journal.pone.0167385
Blacker TS, Mann ZF, Gale JE, Ziegler M, Bain AJ, Szabadkai G, Duchen MR (2014) Separating NADH and NADPH fluorescence in live cells and tissues using FLIM. Nat Commun 5:3936. doi:10.1038/ncomms4936
Stringari C, Cinquin A, Cinquin O, Digman MA, Donovan PJ, Gratton E (2011) Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue. Proc Natl Acad Sci U S A 108(33):13582–13587. doi:10.1073/pnas.1108161108
Jungmann JH, Heeren RM (2012) Emerging technologies in mass spectrometry imaging. J Proteome 75(16):5077–5092. doi:10.1016/j.jprot.2012.03.022
Feist PE, Sidoli S, Liu X, Schroll MM, Rahmy S, Fujiwara R, Garcia BA, Hummon AB (2017) Multicellular tumor spheroids combined with mass spectrometric histone analysis to evaluate epigenetic drugs. Anal Chem 89(5):2773–2781. doi:10.1021/acs.analchem.6b03602
Giordano S, Morosi L, Veglianese P, Licandro SA, Frapolli R, Zucchetti M, Cappelletti G, Falciola L, Pifferi V, Visentin S, D'Incalci M, Davoli E (2016) 3D mass spectrometry imaging reveals a very heterogeneous drug distribution in tumors. Sci Rep 6:37027. doi:10.1038/srep37027
Jiang L, Chughtai K, Purvine SO, Bhujwalla ZM, Raman V, Pasa-Tolic L, Heeren RM, Glunde K (2015) MALDI-mass spectrometric imaging revealing hypoxia-driven lipids and proteins in a breast tumor model. Anal Chem 87(12):5947–5956. doi:10.1021/ac504503x
Psaila B, Lyden D (2009) The metastatic niche: adapting the foreign soil. Nat Rev Cancer 9(4):285–293. doi:10.1038/nrc2621
Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473(7347):298–307. doi:10.1038/nature10144
Shieh AC, Swartz MA (2011) Regulation of tumor invasion by interstitial fluid flow. Phys Biol 8(1):015012. doi:10.1088/1478-3975/8/1/015012
Jean C, Gravelle P, Fournie JJ, Laurent G (2011) Influence of stress on extracellular matrix and integrin biology. Oncogene 30(24):2697–2706. doi:10.1038/onc.2011.27
Csikasz-Nagy A, Escudero LM, Guillaud M, Sedwards S, Baum B, Cavaliere M (2013) Cooperation and competition in the dynamics of tissue architecture during homeostasis and tumorigenesis. Semin Cancer Biol 23(4):293–298. doi:10.1016/j.semcancer.2013.05.009
Butcher DT, Alliston T, Weaver VM (2009) A tense situation: forcing tumour progression. Nat Rev Cancer 9(2):108–122. doi:10.1038/nrc2544
DuFort CC, Paszek MJ, Weaver VM (2011) Balancing forces: architectural control of mechanotransduction. Nat Rev Mol Cell Biol 12(5):308–319. doi:10.1038/nrm3112
Fu BM, Tarbell JM (2013) Mechano-sensing and transduction by endothelial surface glycocalyx: composition, structure, and function. Wiley Interdiscip Rev Syst Biol Med 5(3):381–390. doi:10.1002/wsbm.1211
Sund M, Xie L, Kalluri R (2004) The contribution of vascular basement membranes and extracellular matrix to the mechanics of tumor angiogenesis. APMIS 112(7–8):450–462. doi:10.1111/j.1600-0463.2004.t01-1-apm11207-0806.x
Shen Y, Hou Y, Yao S, Huang P, Yobas L (2015) In vitro epithelial organoid generation induced by substrate nanotopography. Sci Rep 5:9293. doi:10.1038/srep09293
Bignon M, Pichol-Thievend C, Hardouin J, Malbouyres M, Brechot N, Nasciutti L, Barret A, Teillon J, Guillon E, Etienne E, Caron M, Joubert-Caron R, Monnot C, Ruggiero F, Muller L, Germain S (2011) Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane. Blood 118(14):3979–3989. doi:10.1182/blood-2010-10-313296
Yamamura N, Sudo R, Ikeda M, Tanishita K (2007) Effects of the mechanical properties of collagen gel on the in vitro formation of microvessel networks by endothelial cells. Tissue Eng 13(7):1443–1453. doi:10.1089/ten.2006.0333
Asparuhova MB, Secondini C, Ruegg C, Chiquet-Ehrismann R (2015) Mechanism of irradiation-induced mammary cancer metastasis: a role for SAP-dependent Mkl1 signaling. Mol Oncol 9(8):1510–1527. doi:10.1016/j.molonc.2015.04.003
Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, Fong SF, Csiszar K, Giaccia A, Weninger W, Yamauchi M, Gasser DL, Weaver VM (2009) Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139(5):891–906. doi:10.1016/j.cell.2009.10.027
Lu P, Weaver VM, Werb Z (2012) The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol 196(4):395–406. doi:10.1083/jcb.201102147
Yu H, Mouw JK, Weaver VM (2011) Forcing form and function: biomechanical regulation of tumor evolution. Trends Cell Biol 21(1):47–56. doi:10.1016/j.tcb.2010.08.015
Matsumoto T, Yung YC, Fischbach C, Kong HJ, Nakaoka R, Mooney DJ (2007) Mechanical strain regulates endothelial cell patterning in vitro. Tissue Eng 13(1):207–217. doi:10.1089/ten.2006.0058
Hanna M, Liu H, Amir J, Sun Y, Morris SW, Siddiqui MA, Lau LF, Chaqour B (2009) Mechanical regulation of the proangiogenic factor CCN1/CYR61 gene requires the combined activities of MRTF-A and CREB-binding protein histone acetyltransferase. J Biol Chem 284(34):23125–23136. doi:10.1074/jbc.M109.019059
Gjorevski N, Piotrowski AS, Varner VD, Nelson CM (2015) Dynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices. Sci Rep 5:11458. doi:10.1038/srep11458
Mierke CT, Rosel D, Fabry B, Brabek J (2008) Contractile forces in tumor cell migration. Eur J Cell Biol 87(8–9):669–676. doi:10.1016/j.ejcb.2008.01.002
Augsten M (2014) Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment. Front Oncol 4:62. doi:10.3389/fonc.2014.00062
Stanisavljevic J, Loubat-Casanovas J, Herrera M, Luque T, Pena R, Lluch A, Albanell J, Bonilla F, Rovira A, Pena C, Navajas D, Rojo F, Garcia de Herreros A, Baulida J (2015) Snail1-expressing fibroblasts in the tumor microenvironment display mechanical properties that support metastasis. Cancer Res 75(2):284–295. doi:10.1158/0008-5472.CAN-14-1903
Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP, Chaudhry SI, Harrington K, Williamson P, Moeendarbary E, Charras G, Sahai E (2013) Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol 15(6):637–646. doi:10.1038/ncb2756
Goetz JG, Minguet S, Navarro-Lerida I, Lazcano JJ, Samaniego R, Calvo E, Tello M, Osteso-Ibanez T, Pellinen T, Echarri A, Cerezo A, Klein-Szanto AJ, Garcia R, Keely PJ, Sanchez-Mateos P, Cukierman E, Del Pozo MA (2011) Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell 146(1):148–163. doi:10.1016/j.cell.2011.05.040
Erez N, Truitt M, Olson P, Arron ST, Hanahan D (2010) Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell 17(2):135–147. doi:10.1016/j.ccr.2009.12.041
Karagiannis GS, Poutahidis T, Erdman SE, Kirsch R, Riddell RH, Diamandis EP (2012) Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue. Mol Cancer Res (MCR) 10(11):1403–1418. doi:10.1158/1541-7786.MCR-12-0307
Hellstrom M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson AK, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela-Arispe ML, Kalen M, Gerhardt H, Betsholtz C (2007) Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 445(7129):776–780. doi:10.1038/Nature05571
Zeng Q, Li S, Chepeha DB, Giordano TJ, Li J, Zhang H, Polverini PJ, Nor J, Kitajewski J, Wang CY (2005) Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling. Cancer Cell 8(1):13–23. doi:10.1016/j.ccr.2005.06.004
Gjorevski N, Boghaert E, Nelson CM (2012) Regulation of epithelial-mesenchymal transition by transmission of mechanical stress through epithelial tissues. Cancer Microenviron (Official Journal of the International Cancer Microenvironment Society) 5(1):29–38. doi:10.1007/s12307-011-0076-5
Gomez EW, Chen QK, Gjorevski N, Nelson CM (2010) Tissue geometry patterns epithelial-mesenchymal transition via intercellular mechanotransduction. J Cell Biochem 110(1):44–51. doi:10.1002/jcb.22545
Sewell-Loftin MK, Delaughter DM, Peacock JR, Brown CB, Baldwin HS, Barnett JV, Merryman WD (2014) Myocardial contraction and hyaluronic acid mechanotransduction in epithelial-to-mesenchymal transformation of endocardial cells. Biomaterials. doi:S0142–9612(13)01535–4 [pii] 10.1016/j.biomaterials.2013.12.051
Chien S (2008) Role of shear stress direction in endothelial mechanotransduction. Mol Cell Biomech (MCB) 5(1):1–8
Li YS, Haga JH, Chien S (2005) Molecular basis of the effects of shear stress on vascular endothelial cells. J Biomech 38(10):1949–1971. doi:10.1016/j.jbiomech.2004.09.030
Galie PA, Nguyen DH, Choi CK, Cohen DM, Janmey PA, Chen CS (2014) Fluid shear stress threshold regulates angiogenic sprouting. Proc Natl Acad Sci U S A 111(22):7968–7973. doi:10.1073/pnas.1310842111
Vickerman V, Kamm RD (2012) Mechanism of a flow-gated angiogenesis switch: early signaling events at cell-matrix and cell-cell junctions. Integr Biol-Uk 4(8):863–874. doi:10.1039/c2ib00184e
Buchanan CF, Verbridge SS, Vlachos PP, Rylander MN (2014) Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model. Cell Adhes Migr 8(5):517–524. doi:10.4161/19336918.2014.970001
Buchanan CF, Voigt EE, Szot CS, Freeman JW, Vlachos PP, Rylander MN (2014) Three-dimensional microfluidic collagen hydrogels for investigating flow-mediated tumor-endothelial signaling and vascular organization. Tissue Eng Part C Methods 20(1):64–75. doi:10.1089/ten.TEC.2012.0731
Ingber DE (2008) Tensegrity-based mechanosensing from macro to micro. Prog Biophys Mol Biol 97(2–3):163–179. doi:S0079-6107(08)00015-1 [pii] 10.1016/j.pbiomolbio.2008.02.005
Lehoux S, Castier Y, Tedgui A (2006) Molecular mechanisms of the vascular responses to haemodynamic forces. J Intern Med 259(4):381–392. doi:10.1111/j.1365-2796.2006.01624.x
Ngu H, Feng Y, Lu L, Oswald SJ, Longmore GD, Yin FC (2010) Effect of focal adhesion proteins on endothelial cell adhesion, motility and orientation response to cyclic strain. Ann Biomed Eng 38(1):208–222. doi:10.1007/s10439-009-9826-7
Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8(8):604–617. doi:10.1038/Nrc2353
Weinbaum S, Zhang X, Han Y, Vink H, Cowin SC (2003) Mechanotransduction and flow across the endothelial glycocalyx. Proc Natl Acad Sci U S A 100(13):7988–7995. doi:10.1073/pnas.1332808100
Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG (2007) The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch 454(3):345–359. doi:10.1007/s00424-007-0212-8
Pelham RJ Jr, Wang YL (1998) Cell locomotion and focal adhesions are regulated by the mechanical properties of the substrate. Biol Bull 194(3):348–349. discussion 349–350
Pelham RJ Jr, Wang Y (1997) Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci U S A 94(25):13661–13665
Dong Y, Xie X, Wang Z, Hu C, Zheng Q, Wang Y, Chen R, Xue T, Chen J, Gao D, Wu W, Ren Z, Cui J (2014) Increasing matrix stiffness upregulates vascular endothelial growth factor expression in hepatocellular carcinoma cells mediated by integrin beta1. Biochem Biophys Res Commun 444(3):427–432. doi:10.1016/j.bbrc.2014.01.079
Kojima T, Moraes C, Cavnar SP, Luker GD, Takayama S (2015) Surface-templated hydrogel patterns prompt matrix-dependent migration of breast cancer cells towards chemokine-secreting cells. Acta Biomater 13:68–77. doi:10.1016/j.actbio.2014.11.033
Fraley SI, Feng Y, Krishnamurthy R, Kim DH, Celedon A, Longmore GD, Wirtz D (2010) A distinctive role for focal adhesion proteins in three-dimensional cell motility. Nat Cell Biol 12(6):598–604. doi:10.1038/ncb2062
Zebda N, Dubrovskyi O, Birukov KG (2012) Focal adhesion kinase regulation of mechanotransduction and its impact on endothelial cell functions. Microvasc Res 83(1):71–81. doi:10.1016/j.mvr.2011.06.007
Kim DH, Khatau SB, Feng Y, Walcott S, Sun SX, Longmore GD, Wirtz D (2012) Actin cap associated focal adhesions and their distinct role in cellular mechanosensing. Sci Rep 2:555. doi:10.1038/srep00555
Nagelkerke A, Bussink J, Sweep FC, Span PN (2013) Generation of multicellular tumor spheroids of breast cancer cells: how to go three-dimensional. Anal Biochem 437(1):17–19. doi:10.1016/j.ab.2013.02.004
Timmins NE, Nielsen LK (2007) Generation of multicellular tumor spheroids by the hanging-drop method. Methods Mol Med 140:141–151
Skardal A, Devarasetty M, Rodman C, Atala A, Soker S (2015) Liver-tumor hybrid organoids for modeling tumor growth and drug response in vitro. Ann Biomed Eng 43(10):2361–2373. doi:10.1007/s10439-015-1298-3
Fong EL, Wan X, Yang J, Morgado M, Mikos AG, Harrington DA, Navone NM, Farach-Carson MC (2015) A 3D in vitro model of patient-derived prostate cancer xenograft for controlled interrogation of in vivo tumor-stromal interactions. Biomaterials 77:164–172. doi:10.1016/j.biomaterials.2015.10.059
Bates RC, Buret A, van Helden DF, Horton MA, Burns GF (1994) Apoptosis induced by inhibition of intercellular contact. J Cell Biol 125(2):403–415
Takebe T, Enomura M, Yoshizawa E, Kimura M, Koike H, Ueno Y, Matsuzaki T, Yamazaki T, Toyohara T, Osafune K, Nakauchi H, Yoshikawa HY, Taniguchi H (2015) Vascularized and complex organ buds from diverse tissues via mesenchymal cell-driven condensation. Cell Stem Cell 16(5):556–565. doi:10.1016/j.stem.2015.03.004
Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguchi H (2013) Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499(7459):481–484. doi:10.1038/nature12271
Takebe T, Zhang RR, Koike H, Kimura M, Yoshizawa E, Enomura M, Koike N, Sekine K, Taniguchi H (2014) Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant. Nat Protoc 9(2):396–409. doi:10.1038/nprot.2014.020
Verbridge SS, Choi NW, Zheng Y, Brooks DJ, Stroock AD, Fischbach C (2010) Oxygen-controlled three-dimensional cultures to analyze tumor angiogenesis. Tissue Eng Part A 16(7):2133–2141. doi:10.1089/ten.TEA.2009.0670
Kilarski WW, Samolov B, Petersson L, Kvanta A, Gerwins P (2009) Biomechanical regulation of blood vessel growth during tissue vascularization. Nat Med 15(6):657–U145. doi:10.1038/Nm.1985
Liang Y, Jeong J, DeVolder RJ, Cha C, Wang F, Tong YW, Kong H (2011) A cell-instructive hydrogel to regulate malignancy of 3D tumor spheroids with matrix rigidity. Biomaterials 32(35):9308–9315. doi:10.1016/j.biomaterials.2011.08.045
Hsu YH, Moya ML, Abiri P, Hughes CC, George SC, Lee AP (2013) Full range physiological mass transport control in 3D tissue cultures. Lab Chip 13(1):81–89. doi:10.1039/c2lc40787f
Hsu YH, Moya ML, Hughes CC, George SC, Lee AP (2013) A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays. Lab Chip 13(15):2990–2998. doi:10.1039/c3lc50424g
Moya ML, Alonzo LF, George SC (2014) Microfluidic device to culture 3D in vitro human capillary networks. Methods Mol Biol 1202:21–27. doi:10.1007/7651_2013_36
Chung S, Sudo R, Mack PJ, Wan CR, Vickerman V, Kamm RD (2009) Cell migration into scaffolds under co-culture conditions in a microfluidic platform. Lab Chip 9(2):269–275. doi:10.1039/B807585a
Park YK, Tu TY, Lim SH, Clement IJM, Yang SY, Kamm RD (2014) In vitro microvessel growth and remodeling within a three-dimensional microfluidic environment. Cell Mol Bioeng 7(1):15–25. doi:10.1007/s12195-013-0315-6
Sudo R, Chung S, Zervantonakis IK, Vickerman V, Toshimitsu Y, Griffith LG, Kamm RD (2009) Transport-mediated angiogenesis in 3D epithelial coculture. FASEB J 23(7):2155–2164. doi:10.1096/fj.08-122820
Cross MJ, Claesson-Welsh L (2001) FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci 22(4):201–207. doi:10.1016/S0165-6147(00)01676-X
Lee H, Kim S, Chung M, Kim JH, Jeon NL (2014) A bioengineered array of 3D microvessels for vascular permeability assay. Microvasc Res 91:90–98. doi:10.1016/j.mvr.2013.12.001
Alizadeh AM, Shiri S, Farsinejad S (2014) Metastasis review: from bench to bedside. Tumour Biol (The Journal of the International Society for Oncodevelopmental Biology and Medicine) 35(9):8483–8523. doi:10.1007/s13277-014-2421-z
Blazejczyk A, Papiernik D, Porshneva K, Sadowska J, Wietrzyk J (2015) Endothelium and cancer metastasis: perspectives for antimetastatic therapy. Pharmacol Rep (PR) 67(4):711–718. doi:10.1016/j.pharep.2015.05.014
Chang J, Erler J (2014) Hypoxia-mediated metastasis. Adv Exp Med Biol 772:55–81. doi:10.1007/978-1-4614-5915-6_3
Irmisch A, Huelsken J (2013) Metastasis: new insights into organ-specific extravasation and metastatic niches. Exp Cell Res 319(11):1604–1610. doi:10.1016/j.yexcr.2013.02.012
Garcia-Roman J, Zentella-Dehesa A (2013) Vascular permeability changes involved in tumor metastasis. Cancer Lett 335(2):259–269. doi:10.1016/j.canlet.2013.03.005
Miles FL, Pruitt FL, van Golen KL, Cooper CR (2008) Stepping out of the flow: capillary extravasation in cancer metastasis. Clin Exp Metastasis 25(4):305–324. doi:10.1007/s10585-007-9098-2
Reymond N, d’Agua BB, Ridley AJ (2013) Crossing the endothelial barrier during metastasis. Nat Rev Cancer 13(12):858–870. doi:10.1038/nrc3628
van Zijl F, Krupitza G, Mikulits W (2011) Initial steps of metastasis: cell invasion and endothelial transmigration. Mutat Res 728(1–2):23–34. doi:10.1016/j.mrrev.2011.05.002
Bersini S, Jeon JS, Moretti M, Kamm RD (2014) In vitro models of the metastatic cascade: from local invasion to extravasation. Drug Discov Today 19(6):735–742. doi:10.1016/j.drudis.2013.12.006
Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820–827. doi:10.1038/nature04186
Ghajar CM, Peinado H, Mori H, Matei IR, Evason KJ, Brazier H, Almeida D, Koller A, Hajjar KA, Stainier DYR, Chen EI, Lyden D, Bissell MJ (2013) The perivascular niche regulates breast tumour dormancy. Nat Cell Biol 15(7):807–817. doi:10.1038/ncb2767. http://www.nature.com/ncb/journal/v15/n7/abs/ncb2767.html#supplementary-information
Lee H, Park W, Ryu H, Jeon NL (2014) A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation. Biomicrofluidics 8(5):054102. doi:10.1063/1.4894595
Zervantonakis IK, Hughes-Alford SK, Charest JL, Condeelis JS, Gertler FB, Kamm RD (2012) Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proc Natl Acad Sci U S A 109(34):13515–13520. doi:10.1073/pnas.1210182109
Camerer E, Qazi AA, Duong DN, Cornelissen I, Advincula R, Coughlin SR (2004) Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood 104(2):397–401. doi:10.1182/blood-2004-02-0434
Coupland LA, Chong BH, Parish CR (2012) Platelets and P-selectin control tumor cell metastasis in an organ-specific manner and independently of NK cells. Cancer Res 72(18):4662–4671. doi:10.1158/0008-5472.CAN-11-4010
Reymond N, Im JH, Garg R, Vega FM, Borda d'Agua B, Riou P, Cox S, Valderrama F, Muschel RJ, Ridley AJ (2012) Cdc42 promotes transendothelial migration of cancer cells through beta1 integrin. J Cell Biol 199(4):653–668. doi:10.1083/jcb.201205169
Shirure VS, Liu T, Delgadillo LF, Cuckler CM, Tees DF, Benencia F, Goetz DJ, Burdick MM (2015) CD44 variant isoforms expressed by breast cancer cells are functional E-selectin ligands under flow conditions. Am J Physiol Cell Physiol 308(1):C68–C78. doi:10.1152/ajpcell.00094.2014
Jeon JS, Zervantonakis IK, Chung S, Kamm RD, Charest JL (2013) In vitro model of tumor cell extravasation. PLoS One 8(2):e56910. doi:10.1371/journal.pone.0056910
Heyder C, Gloria-Maercker E, Entschladen F, Hatzmann W, Niggemann B, Zanker KS, Dittmar T (2002) Realtime visualization of tumor cell/endothelial cell interactions during transmigration across the endothelial barrier. J Cancer Res Clin Oncol 128(10):533–538. doi:10.1007/s00432-002-0377-7
Nolan DJ, Ginsberg M, Israely E, Palikuqi B, Poulos MG, James D, Ding BS, Schachterle W, Liu Y, Rosenwaks Z, Butler JM, Xiang J, Rafii A, Shido K, Rabbany SY, Elemento O, Rafii S (2013) Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev Cell 26(2):204–219. doi:10.1016/j.devcel.2013.06.017
Moya ML, George SC (2014) Integrating organ-specific function with the microcirculation. Curr Opin Chem Eng 3:103–111. doi:10.1016/j.coche.2013.12.004
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Shirure, V.S., Sewell-Loftin, M.K., Lam, S.F., Todd, T.D., Hwang, P.Y., George, S.C. (2018). Building Better Tumor Models: Organoid Systems to Investigate Angiogenesis. In: Soker, S., Skardal, A. (eds) Tumor Organoids. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-60511-1_7
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