Skip to main content
SpringerLink
Log in

Brain Metastases Cell Partners and Tumor Microenvironment

  • Chapter
  • First Online:
Central Nervous System Metastases

  • 1093 Accesses

Abstract

The microenvironment has emerged as a promising source of novel therapeutic applications in experimental models of brain metastasis. Our limited understanding of the complex brain ecosystem transformed by the presence of cancer cells includes key cell types that either promote or limit local progression of metastatic cells. Identification of the molecular networks regulating the crosstalk between cancer cells and the microenvironment but also within different brain resident and non-resident cell types surrounding the tumor is crucial to decipher the biology of colonization and subsequently to target key nodes with innovative and effective therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kienast Y, von Baumgarten L, Fuhrmann M, Klinkert WEF, Goldbrunner R, Herms J, et al. Real-time imaging reveals the single steps of brain metastasis formation. Nat Med. 2010;16(1):116–22.

    Article  CAS  PubMed  Google Scholar 

  2. Follain G, Osmani N, Azevedo AS, Allio G, Mercier L, Karreman MA, et al. Hemodynamic forces tune the arrest, adhesion, and extravasation of circulating tumor cells. Dev Cell. 2018;45(1):33–52.. e12

    Article  CAS  PubMed  Google Scholar 

  3. Er EE, Valiente M, Ganesh K, Zou Y, Agrawal S, Hu J, et al. Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization. Nat Cell Biol. 2018;20(8):966–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XH-F, Lee DJ, et al. Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell. 2014;156(5):1002–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bos PD, Zhang XH-F, Nadal C, Shu W, Gomis RR, Nguyen DX, et al. Genes that mediate breast cancer metastasis to the brain. Nature. 2009;459(7249):1005–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sevenich L, Bowman RL, Mason SD, Quail DF, Rapaport F, Elie BT, et al. Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S. Nat Cell Biol. 2014 Sep;16(9):876–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Li B, Wang C, Zhang Y, Zhao XY, Huang B, Wu PF, et al. Elevated PLGF contributes to small-cell lung cancer brain metastasis. Oncogene. 2013;32(24):2952–62.

    Article  CAS  PubMed  Google Scholar 

  8. Tominaga N, Kosaka N, Ono M, Katsuda T, Yoshioka Y, Tamura K, et al. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier. Nat Commun. 2015;6:6716.

    Article  CAS  PubMed  Google Scholar 

  9. Zhou W, Fong MY, Min Y, Somlo G, Liu L, Palomares MR, et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell. 2014;25(4):501–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bobrie A, Krumeich S, Reyal F, Recchi C, Moita LF, Seabra MC, et al. Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res. 2012;72(19):4920–30.

    Article  CAS  PubMed  Google Scholar 

  11. Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 2012;18(6):883–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–9.

    Article  CAS  PubMed  Google Scholar 

  13. Jilaveanu LB, Parisi F, Barr ML, Zito CR, Cruz-Munoz W, Kerbel RS, et al. PLEKHA5 as a biomarker and potential mediator of melanoma brain metastasis. Clin Cancer Res. 2015;21(9):2138–47.

    Article  CAS  PubMed  Google Scholar 

  14. Carbonell WS, Ansorge O, Sibson N, Muschel R. The vascular basement membrane as “soil” in brain metastasis. PLoS One. 2009;4(6):e5857.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999;284(5422):1994–8.

    Article  CAS  PubMed  Google Scholar 

  16. Bentolila LA, Prakash R, Mihic-Probst D, Wadehra M, Kleinman HK, Carmichael TS, et al. Imaging of angiotropism/vascular co-option in a murine model of brain melanoma: implications for melanoma progression along extravascular pathways. Sci Rep. 2016;6(1):23834.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Berghoff AS, Rajky O, Winkler F, Bartsch R, Furtner J, Hainfellner JA, et al. Invasion patterns in brain metastases of solid cancers. Neuro-Oncology. 2013;15(12):1664–72.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Lorger M, Felding-Habermann B. Capturing changes in the brain microenvironment during initial steps of breast cancer brain metastasis. Am J Pathol. 2010;176(6):2958–71.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Nguyen DX, Chiang AC, Zhang XH-F, Kim JY, Kris MG, Ladanyi M, et al. WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell. 2009;138(1):51–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rafii S, Butler JM, Ding B-S. Angiocrine functions of organ-specific endothelial cells. Nature. 2016;529(7586):316–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Malladi S, Macalinao DG, Jin X, He L, Basnet H, Zou Y, et al. Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell. 2016;165(1):45–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ghajar CM, Peinado H, Mori H, Matei IR, Evason KJ, Brazier H, et al. The perivascular niche regulates breast tumour dormancy. Nat Cell Biol. 2013;15(7):807–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836–46.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Goss PE, Chambers AF. Does tumour dormancy offer a therapeutic target? Nat Rev Cancer. 2010;10(12):871–7.

    Article  CAS  PubMed  Google Scholar 

  25. Lawler J. Thrombospondin-1 as an endogenous inhibitor of angiogenesis and tumor growth. J Cell Mol Med. 2002;6(1):1–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Weinstat-Saslow DL, Zabrenetzky VS, VanHoutte K, Frazier WA, Roberts DD, Steeg PS. Transfection of thrombospondin 1 complementary DNA into a human breast carcinoma cell line reduces primary tumor growth, metastatic potential, and angiogenesis. Cancer Res. 1994;54(24):6504–11.

    CAS  PubMed  Google Scholar 

  27. Yano S, Shinohara H, Herbst RS, Kuniyasu H, Bucana CD, Ellis LM, et al. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Res. 2000;60(17):4959–67.

    CAS  PubMed  Google Scholar 

  28. Kim LS, Huang S, Lu W, Lev DC, Price JE. Vascular endothelial growth factor expression promotes the growth of breast cancer brain metastases in nude mice. Clin Exp Metastasis. 2004;21(2):107–18.

    Article  CAS  PubMed  Google Scholar 

  29. Kodack DP, Chung E, Yamashita H, Incio J, Duyverman AMMJ, Song Y, et al. Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases. Proc Natl Acad Sci U S A. 2012;109(45):E3119–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219(4587):983–5.

    Article  CAS  PubMed  Google Scholar 

  31. Lorger M, Krueger JS, O’Neal M, Staflin K, Felding-Habermann B. Activation of tumor cell integrin alphavbeta3 controls angiogenesis and metastatic growth in the brain. Proc Natl Acad Sci U S A. 2009;106(26):10666–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jain RK. Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell. 2014;26(5):605–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jahangiri A, Nguyen A, Chandra A, Sidorov MK, Yagnik G, Rick J, et al. Cross-activating c-Met/β1 integrin complex drives metastasis and invasive resistance in cancer. Proc Natl Acad Sci U S A. 2017;114(41):E8685–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rojiani MV, Alidina J, Esposito N, Rojiani AM. Expression of MMP-2 correlates with increased angiogenesis in CNS metastasis of lung carcinoma. Int J Clin Exp Pathol. 2010;3(8):775–81.

    PubMed  PubMed Central  Google Scholar 

  35. Ilhan-Mutlu A, Osswald M, Liao Y, Gömmel M, Reck M, Miles D, et al. Bevacizumab prevents brain metastases formation in lung adenocarcinoma. Mol Cancer Ther. 2016;15(4):702–10.

    Article  CAS  PubMed  Google Scholar 

  36. Ilhan-Mutlu A, Siehs C, Berghoff AS, Ricken G, Widhalm G, Wagner L, et al. Expression profiling of angiogenesis-related genes in brain metastases of lung cancer and melanoma. Tumour Biol. 2016;37(1):1173–82.

    Article  CAS  PubMed  Google Scholar 

  37. Jubb AM, Cesario A, Ferguson M, Congedo MT, Gatter KC, Lococo F, et al. Vascular phenotypes in primary non-small cell lung carcinomas and matched brain metastases. Br J Cancer. 2011;104(12):1877–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bohn KA, Adkins CE, Nounou MI, Lockman PR. Inhibition of VEGF and angiopoietin-2 to reduce brain metastases of breast cancer burden. Front Pharmacol. 2017;8:193.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. de Lange ECM, Hammarlund-Udenaes M. Translational aspects of blood-brain barrier transport and central nervous system effects of drugs: from discovery to patients. Clin Pharmacol Ther. 2015;97(4):380–94.

    Article  PubMed  Google Scholar 

  40. Phoenix TN, Patmore DM, Boop S, Boulos N, Jacus MO, Patel YT, et al. Medulloblastoma genotype dictates blood brain barrier phenotype. Cancer Cell. 2016;29(4):508–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lockman PR, Mittapalli RK, Taskar KS, Rudraraju V, Gril B, Bohn KA, et al. Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res. 2010;16(23):5664–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Osswald M, Blaes J, Liao Y, Solecki G, Gömmel M, Berghoff AS, et al. Impact of blood-brain barrier integrity on tumor growth and therapy response in brain metastases. Clin Cancer Res. 2016;22(24):6078–87.

    Article  CAS  PubMed  Google Scholar 

  43. Arvanitis CD, Askoxylakis V, Guo Y, Datta M, Kloepper J, Ferraro GB, et al. Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood-tumor barrier disruption. Proc Natl Acad Sci U S A. 2018 Aug 27;115:E8717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lyle LT, Lockman PR, Adkins CE, Mohammad AS, Sechrest E, Hua E, et al. Alterations in pericyte subpopulations are associated with elevated blood-tumor barrier permeability in experimental brain metastasis of breast cancer. Clin Cancer Res. 2016;22(21):5287–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 2009;32(12):638–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Xing F, Liu Y, Sharma S, Wu K, Chan MD, Lo H-W, et al. Activation of the c-met pathway mobilizes an inflammatory network in the brain microenvironment to promote brain metastasis of breast cancer. Cancer Res. 2016;76(17):4970–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Xing F, Kobayashi A, Okuda H, Watabe M, Pai SK, Pandey PR, et al. Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain. EMBO Mol Med. 2013;5(3):384–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Seike T, Fujita K, Yamakawa Y, Kido MA, Takiguchi S, Teramoto N, et al. Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis. Clin Exp Metastasis. 2011 Jan;28(1):13–25.

    Article  CAS  PubMed  Google Scholar 

  49. Choy C, Ansari KI, Neman J, Hsu S, Duenas MJ, Li H, et al. Cooperation of neurotrophin receptor TrkB and Her2 in breast cancer cells facilitates brain metastases. Breast Cancer Res. 2017;19(1):51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Klein A, Schwartz H, Sagi-Assif O, Meshel T, Izraely S, Ben Menachem S, et al. Astrocytes facilitate melanoma brain metastasis via secretion of IL-23. J Pathol. 2015;236(1):116–27.

    Article  CAS  PubMed  Google Scholar 

  51. Schwartz H, Blacher E, Amer M, Livneh N, Abramovitz L, Klein A, et al. Incipient melanoma brain metastases instigate astrogliosis and neuroinflammation. Cancer Res. 2016;76(15):4359–71.

    Article  CAS  PubMed  Google Scholar 

  52. Shumakovich MA, Mencio CP, Siglin JS, Moriarty RA, Geller HM, Stroka KM. Astrocytes from the brain microenvironment alter migration and morphology of metastatic breast cancer cells. FASEB J. 2017;31:5049.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Lin Q, Balasubramanian K, Fan D, Kim S-J, Guo L, Wang H, et al. Reactive astrocytes protect melanoma cells from chemotherapy by sequestering intracellular calcium through gap junction communication channels. Neoplasia. 2010;12(9):748–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kim S-J, Kim J-S, Park ES, Lee J-S, Lin Q, Langley RR, et al. Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy. Neoplasia. 2011;13(3):286–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chen Q, Boire A, Jin X, Valiente M, Er EE, Lopez-Soto A, et al. Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature. 2016;533(7604):493–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhang L, Zhang S, Yao J, Lowery FJ, Zhang Q, Huang W-C, et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature. 2015;527(7576):100–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gril B, Palmieri D, Qian Y, Anwar T, Liewehr DJ, Steinberg SM, et al. Pazopanib inhibits the activation of PDGFRβ-expressing astrocytes in the brain metastatic microenvironment of breast cancer cells. Am J Pathol. 2013;182(6):2368–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Priego N, Zhu L, Monteiro C, Mulders M, Wasilewski D, Bindeman W, et al. STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat Med. 2018;24(7):1024–35.

    Article  CAS  PubMed  Google Scholar 

  59. Goldmann T, Wieghofer P, Jordão MJC, Prutek F, Hagemeyer N, Frenzel K, et al. Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat Immunol. 2016;17(7):797–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bowman RL, Klemm F, Akkari L, Pyonteck SM, Sevenich L, Quail DF, et al. Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies. Cell Rep. 2016;17(9):2445–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Davis EJ, Foster TD, Thomas WE. Cellular forms and functions of brain microglia. Brain Res Bull. 1994;34(1):73–8.

    Article  CAS  PubMed  Google Scholar 

  62. Fitzgerald DP, Palmieri D, Hua E, Hargrave E, Herring JM, Qian Y, et al. Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization. Clin Exp Metastasis. 2008;25(7):799–810.

    Article  PubMed  PubMed Central  Google Scholar 

  63. He BP, Wang JJ, Zhang X, Wu Y, Wang M, Bay B-H, et al. Differential reactions of microglia to brain metastasis of lung cancer. Mol Med. 2006;12(7–8):161–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Pukrop T, Dehghani F, Chuang H-N, Lohaus R, Bayanga K, Heermann S, et al. Microglia promote colonization of brain tissue by breast cancer cells in a Wnt-dependent way. Glia. 2010;58(12):1477–89.

    Article  PubMed  Google Scholar 

  65. Izraely S, Ben-Menachem S, Sagi-Assif O, Telerman A, Zubrilov I, Ashkenazi O, et al. The metastatic microenvironment: melanoma-microglia cross-talk promotes the malignant phenotype of melanoma cells. Int J Cancer. 2019;144(4):802–17.

    Article  CAS  PubMed  Google Scholar 

  66. Amit M, Laider-Trejo L, Shalom V, Shabtay-Orbach A, Krelin Y, Gil Z. Characterization of the melanoma brain metastatic niche in mice and humans. Cancer Med. 2013;2(2):155–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, Fernhoff NB, et al. New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci U S A. 2016;113(12):E1738–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Morantz RA, Wood GW, Foster M, Clark M, Gollahon K. Macrophages in experimental and human brain tumors. Part 2: studies of the macrophage content of human brain tumors. J Neurosurg. 1979;50(3):305–11.

    Article  CAS  PubMed  Google Scholar 

  69. Rippaus N, Taggart D, Williams J, Andreou T, Wurdak H, Wronski K, et al. Metastatic site-specific polarization of macrophages in intracranial breast cancer metastases. Oncotarget. 2016;7(27):41473–87.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Louie E, Chen XF, Coomes A, Ji K, Tsirka S, Chen EI. Neurotrophin-3 modulates breast cancer cells and the microenvironment to promote the growth of breast cancer brain metastasis. Oncogene. 2013;32(35):4064–77.

    Article  CAS  PubMed  Google Scholar 

  71. Brantley EC, Guo L, Zhang C, Lin Q, Yokoi K, Langley RR, et al. Nitric oxide-mediated tumoricidal activity of murine microglial cells. Transl Oncol. 2010;3(6):380–8.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Hanisch U-K, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10(11):1387–94.

    Article  CAS  PubMed  Google Scholar 

  73. Tzeng S-F, Huang H-Y, Lee T-I, Jwo J-K. Inhibition of lipopolysaccharide-induced microglial activation by preexposure to neurotrophin-3. J Neurosci Res. 2005;81(5):666–76.

    Article  CAS  PubMed  Google Scholar 

  74. Hohensee I, Chuang H-N, Grottke A, Werner S, Schulte A, Horn S, et al. PTEN mediates the cross talk between breast and glial cells in brain metastases leading to rapid disease progression. Oncotarget. 2017;8(4):6155–68.

    Article  PubMed  Google Scholar 

  75. Chuang H-N, van Rossum D, Sieger D, Siam L, Klemm F, Bleckmann A, et al. Carcinoma cells misuse the host tissue damage response to invade the brain. Glia. 2013;61(8):1331–46.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Prinz M, Erny D, Hagemeyer N. Ontogeny and homeostasis of CNS myeloid cells. Nat Immunol. 2017;18(4):385–92.

    Article  CAS  PubMed  Google Scholar 

  77. Xiong Z, Gharagozlou S, Vengco I, Chen W, Ohlfest JR. Effective CpG immunotherapy of breast carcinoma prevents but fails to eradicate established brain metastasis. Clin Cancer Res. 2008;14(17):5484–93.

    Article  CAS  PubMed  Google Scholar 

  78. Xia L, Wu H, Qian W. Irradiation enhanced the effects of PD-1 blockade in brain metastatic osteosarcoma. J Bone Oncol. 2018;12:61–4.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Sampson JH, Archer GE, Ashley DM, Fuchs HE, Hale LP, Dranoff G, et al. Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the “immunologically privileged” central nervous system. Proc Natl Acad Sci U S A. 1996;93(19):10399–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lu W, Su J, Kim LS, Bucana CD, Donawho C, He J, et al. Active specific immunotherapy against occult brain metastasis. Cancer Res. 2003;63(6):1345–50.

    CAS  PubMed  Google Scholar 

  81. Yagiz K, Rodriguez-Aguirre ME, Lopez Espinoza F, Montellano TT, Mendoza D, Mitchell LA, et al. A retroviral replicating vector encoding cytosine deaminase and 5-FC induces immune memory in metastatic colorectal cancer models. Mol Ther Oncolytics. 2018;8:14–26.

    Article  CAS  PubMed  Google Scholar 

  82. Liu Y, Komohara Y, Domenick N, Ohno M, Ikeura M, Hamilton RL, et al. Expression of antigen processing and presenting molecules in brain metastasis of breast cancer. Cancer Immunol Immunother. 2012;61(6):789–801.

    Article  CAS  PubMed  Google Scholar 

  83. Taggart D, Andreou T, Scott KJ, Williams J, Rippaus N, Brownlie RJ, et al. Anti-PD-1/anti-CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8+ T cell trafficking. Proc Natl Acad Sci U S A. 2018;115(7):E1540–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Broder H, Anderson A, Kremen TJ, Odesa SK, Liau LM. MART-1 adenovirus-transduced dendritic cell immunization in a murine model of metastatic central nervous system tumor. J Neuro-Oncol. 2003;64(1–2):21–30.

    Google Scholar 

  85. Priceman SJ, Tilakawardane D, Jeang B, Aguilar B, Murad JP, Park AK, et al. Regional delivery of chimeric antigen receptor-engineered T cells effectively targets HER2+ breast cancer metastasis to the brain. Clin Cancer Res. 2018;24(1):95–105.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Research in the Brain Metastasis Group is supported by MINECO grants MINECO-Retos SAF2017-89643-R (M.V.), Bristol-Myers Squibb-Melanoma Research Alliance Young Investigator Award 2017 (498103) (M.V.), Beug Foundation’s Prize for Metastasis Research 2017 (M.V.), Fundación Ramón Areces (CIVP19S8163) (M.V.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972) (M.V.), Clinic and Laboratory Integration Program CRI Award 2018 (54545) (M.V.), AECC Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002VALI) (M.V.), AECC Postdoctoral Grant (POSTD19016PRIE) (N.P.), La Caixa INPhINIT Fellowship (100010434) (P.G-G.), MINECO-Severo Ochoa PhD Fellowship (BES-2017-081995) (L.A-E.). M.V. is a Ramón y Cajal Investigator (RYC-2013-13365) and EMBO YIP (4053).

Author information

Author notes

  1. Pedro García-Gómez, Neibla Priego, and Laura Álvaro-Espinosa contributed equally to this work.

Authors and Affiliations

  1. Brain Metastasis Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain

    Pedro García-Gómez, Neibla Priego, Laura Álvaro-Espinosa & Manuel Valiente

Authors
  1. Pedro García-Gómez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neibla Priego
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura Álvaro-Espinosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manuel Valiente
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manuel Valiente .

Editor information

Editors and Affiliations

  1. Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA

    Manmeet Ahluwalia

  2. Department of Neurosurgery and Neuro-Oncology, Clairval Hospital Center, Ramsay-Générale de Santé, Marseille, France, Neurophysiopathology Institute, Aix-Marseille Université, Marseille, France

    Philippe Metellus

  3. Department of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy

    Riccardo Soffietti

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

García-Gómez, P., Priego, N., Álvaro-Espinosa, L., Valiente, M. (2020). Brain Metastases Cell Partners and Tumor Microenvironment. In: Ahluwalia, M., Metellus, P., Soffietti, R. (eds) Central Nervous System Metastases. Springer, Cham. https://doi.org/10.1007/978-3-030-23417-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-23417-1_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-23416-4

  • Online ISBN: 978-3-030-23417-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation