Abstract
Human lung cancer is one of the leading causes of death worldwide, with nearly 2 million of new cases diagnosed each year, often too late for a successful therapeutic intervention. In this chapter, organotypic models of lung cancer will be reviewed. Ex vivo tissue explants, spheroids, organoids, and novel bioengineering approaches are currently being used to study human lung cancer. Although there is no ideal method that will fully recapitulate the complex human lung architecture, the three-dimensional (3D) organotypic models described here represent a major advance from classical two-dimensional (2D) tissue culture models. Organotypic tissue cultures are better at predicting in vivo tissue responses to anticancer drugs or carcinogenic toxins. In addition, there is also a possibility to use these systems as part of personalized medicine (e.g., to assist clinicians in selecting appropriate therapeutic choices based on individual patient-derived tissue responses to drugs in vitro). There is still a need for improvement in the 3D culture systems, such as automation for high-throughput testing and reduction of costs. However, given the large number of failed clinical trials due to safety or efficacy reasons, more attention should be given to these more physiologically relevant 3D organotypic tissue culture models.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abdull Razis AF, Bagatta M, De Nicola GR, Iori R, Ioannides C (2011) Up-regulation of cytochrome P450 and phase II enzyme systems in rat precision-cut rat lung slices by the intact glucosinolates, glucoraphanin and glucoerucin. Lung Cancer 71:298–305. https://doi.org/10.1016/j.lungcan.2010.06.015
Ahn J, Sei Y, Jeon N, Kim Y (2017) Tumor microenvironment on a chip: the progress and future perspective. Bioengineering 4:64
Amann A et al (2014) Development of an innovative 3D cell culture system to study tumour—stroma interactions in non-small cell lung cancer cells. PLoS ONE 9:e92511. https://doi.org/10.1371/journal.pone.0092511
Aufderheide M, Förster C, Beshay M, Branscheid D, Emura M (2016) A new computer-controlled air–liquid interface cultivation system for the generation of differentiated cell cultures of the airway epithelium. Exp Toxicol Pathol 68:77–87. https://doi.org/10.1016/j.etp.2015.10.001
Baker BM, Chen CS (2012) Deconstructing the third dimension: how 3D culture microenvironments alter cellular cues. J Cell Sci 125:3015–3024. https://doi.org/10.1242/jcs.079509
Balharry D, Sexton K, BeruBe KA (2008) An in vitro approach to assess the toxicity of inhaled tobacco smoke components: nicotine, cadmium, formaldehyde and urethane. Toxicology 244:66–76. https://doi.org/10.1016/j.tox.2007.11.001
Barkauskas CE, Chung MI, Fioret B, Gao X, Katsura H, Hogan BL (2017) Lung organoids: current uses and future promise Development (Cambridge, England) 144:986–997. https://doi.org/10.1242/dev.140103
Barrera-RodrÃguez R, Fuentes JM (2015) Multidrug resistance characterization in multicellular tumour spheroids from two human lung cancer cell lines. Cancer Cell Int 15:47. https://doi.org/10.1186/s12935-015-0200-6
Barrila J, Radtke AL, Crabbé A, Sarker SF, Herbst-Kralovetz MM, Ott CM, Nickerson CA (2010) Organotypic 3D cell culture models: using the rotating wall vessel to study host–pathogen interactions. Nat Rev Micro 8:791–801
Behrsing HP, Furniss MJ, Davis M, Tomaszewski JE, Parchment RE (2013) In vitro exposure of precision-cut lung slices to 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole lysylamide dihydrochloride (NSC 710305, Phortress) increases inflammatory cytokine content and tissue damage. Toxicol Sci 131:470–479. https://doi.org/10.1093/toxsci/kfs319
Bhatia SN, Ingber DE (2014) Microfluidic organs-on-chips. Nat Biotech 32:760–772. https://doi.org/10.1038/nbt.2989
Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong K-K (2014) Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer 14:535. https://doi.org/10.1038/nrc3775
Chen XW, Sun JG, Zhang LP, Liao XY, Liao RX (2017a) Recruitment of CD11b+ Ly6C+ monocytes in non-small cell lung cancer xenografts challenged by anti-VEGF antibody Oncol Lett 14:615–622. https://doi.org/10.3892/ol.2017.6236
Chen Y-W et al (2017b) A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat Cell Biol 19:542–549. https://doi.org/10.1038/ncb3510
Chimenti I et al (2017) Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties. STEM CELLS Transl Med 6:767–777. https://doi.org/10.5966/sctm.2015-0374
Cooper PR, Panettieri RA Jr (2008) Steroids completely reverse albuterol-induced beta(2)-adrenergic receptor tolerance in human small airways. J Allergy Clin Immunol 122:734–740. https://doi.org/10.1016/j.jaci.2008.07.040
Cooper PR et al (2009) TLR3 activation stimulates cytokine secretion without altering agonist-induced human small airway contraction or relaxation. Am J Physiol Lung Cell Mol Physiol 297:L530–537. https://doi.org/10.1152/ajplung.00133.2009
Cooper PR, Poll CT, Barnes PJ, Sturton RG (2010) Involvement of IL-13 in tobacco smoke-induced changes in the structure and function of rat intrapulmonary airways. Am J Respir Cell Mol Biol 43:220–226. https://doi.org/10.1165/rcmb.2009-0117OC
Cooper PR, Kurten RC, Zhang J, Nicholls DJ, Dainty IA, Panettieri RA (2011a) Formoterol and salmeterol induce a similar degree of beta2-adrenoceptor tolerance in human small airways but via different mechanisms. Br J Pharmacol 163:521–532. https://doi.org/10.1111/j.1476-5381.2011.01257.x
Cooper PR, Zhang J, Damera G, Hoshi T, Zopf DA, Panettieri RA Jr (2011b) C-027 inhibits IgE-mediated passive sensitization bronchoconstriction and acts as a histamine and serotonin antagonist in human airways. Allergy Asthma Proc 32:359–365. https://doi.org/10.2500/aap.2011.32.3460
Danahay H et al (2015) Notch2 Is required for inflammatory cytokine-driven goblet cell metaplasia in the lung. Cell Reports 10:239–252. https://doi.org/10.1016/j.celrep.2014.12.017
Deslee G et al (2007) Bronchial epithelial spheroids: an alternative culture model to investigate epithelium inflammation-mediated COPD. Respir Res 8:86. https://doi.org/10.1186/1465-9921-8-86
Dinh P-UC et al (2017) Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies. Respir Res 18:132. https://doi.org/10.1186/s12931-017-0611-0
Donovan C et al (2015) Rosiglitazone elicits in vitro relaxation in airways and precision cut lung slices from a mouse model of chronic allergic airways disease. Am J Physiol Lung Cell Mol Physiol 309:L1219–1228. https://doi.org/10.1152/ajplung.00156.2015
Donovan C, Seow HJ, Bourke JE, Vlahos R (2016) Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to beta-adrenoceptor agonists in mouse lung. Clin Sci (Lond) 130:829–837. https://doi.org/10.1042/cs20160093
Dwivedi AM, Upadhyay S, Johanson G, Ernstgard L, Palmberg L (2017) Inflammatory effects of acrolein, crotonaldehyde and hexanal vapors on human primary bronchial epithelial cells cultured at air-liquid interface Toxicol. In Vitro. https://doi.org/10.1016/j.tiv.2017.09.016
Ebsen M, Mogilevski G, Anhenn O, Maiworm V, Theegarten D, Schwarze J, Morgenroth K (2002) Infection of murine precision cut lung slices (PCLS) with respiratory syncytial virus (RSV) and chlamydophila pneumoniae using the Krumdieck technique. Pathol Res Pract 198:747–753. https://doi.org/10.1078/0344-0338-00331
Ekert JE, Johnson K, Strake B, Pardinas J, Jarantow S, Perkinson R, Colter DC (2014) Three-dimensional lung tumor microenvironment modulates therapeutic compound responsiveness in vitro—implication for drug development. PLoS ONE 9:e92248. https://doi.org/10.1371/journal.pone.0092248
Endo H et al (2013) Spheroid culture of primary lung cancer cells with neuregulin 1/HER3 pathway activation. J Thoracic Oncol Official Publ Int Assoc Study Lung Cancer 8:131–139. https://doi.org/10.1097/JTO.0b013e3182779ccf
Eramo A et al (2007) Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 15:504–514
Esch EW, Bahinski A, Huh D (2015) Organs-on-chips at the frontiers of drug discovery. Nat Rev Drug Discov 14:248–260. https://doi.org/10.1038/nrd4539
Fatehullah A, Tan SH, Barker N (2016) Organoids as an in vitro model of human development and disease. Nat Cell Biol 18:246–254. https://doi.org/10.1038/ncb3312
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F (2013) GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. International Agency for Research on Cancer. http://globocan.iarc.fr. Accessed 04/09/2017
Ferlay J et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–386. https://doi.org/10.1002/ijc.29210
Fessart D, Begueret H, Delom F (2013) Three-dimensional culture model to distinguish normal from malignant human bronchial epithelial cells. Eur Respir J 42:1345–1356. https://doi.org/10.1183/09031936.00118812
Geles KG, Zhong W, O’Brien SK, Baxter M, Loreth C, Pallares D, Damelin M (2016) Upregulation of RNA processing factors in poorly differentiated lung cancer cells. Transl Oncol 9:89–98. https://doi.org/10.1016/j.tranon.2016.01.006
Gray TE, Guzman K, Davis CW, Abdullah LH, Nettesheim P (1996) Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells. Am J Respir Cell Mol Biol 14:104–112. https://doi.org/10.1165/ajrcmb.14.1.8534481
Gridelli C et al (2015) Non-small-cell lung cancer. Nat Rev Dis Primers 1:15009. https://doi.org/10.1038/nrdp.2015.9
Hackett TL, Holloway R, Holgate ST, Warner JA (2008) Dynamics of pro-inflammatory and anti-inflammatory cytokine release during acute inflammation in chronic obstructive pulmonary disease: an ex vivo study. Respir Res 9:47. https://doi.org/10.1186/1465-9921-9-47
Harrigan JA, Vezina CM, McGarrigle BP, Ersing N, Box HC, Maccubbin AE, Olson JR (2004) DNA adduct formation in precision-cut rat liver and lung slices exposed to benzo[a]pyrene. Toxicol Sci 77:307–314. https://doi.org/10.1093/toxsci/kfh030
Harrison RK (2016) Phase II and phase III failures: 2013–2015. Nat Rev Drug Discov 15:817–818. https://doi.org/10.1038/nrd.2016.184
Henjakovic M et al (2008a) Ex vivo lung function measurements in precision-cut lung slices (PCLS) from chemical allergen-sensitized mice represent a suitable alternative to in vivo studies. Toxicol Sci 106:444–453. https://doi.org/10.1093/toxsci/kfn178
Henjakovic M et al (2008b) Ex vivo testing of immune responses in precision-cut lung slices. Toxicol Appl Pharmacol 231:68–76. https://doi.org/10.1016/j.taap.2008.04.003
Henry E et al (2015) Adult lung spheroid cells contain progenitor cells and mediate regeneration in rodents with bleomycin-induced pulmonary fibrosis. Stem Cells Transl Med 4:1265–1274. https://doi.org/10.5966/sctm.2015-0062
Herbert J, Thiermann H, Worek F, Wille T (2017) Precision cut lung slices as test system for candidate therapeutics in organophosphate poisoning. Toxicology 389:94–100. https://doi.org/10.1016/j.tox.2017.07.011
Hess A et al (2016) Prevalidation of the ex-vivo model PCLS for prediction of respiratory toxicity. Toxicol In Vitro 32:347–361. https://doi.org/10.1016/j.tiv.2016.01.006
Hofmann F, Blasche R, Kasper M, Barth K (2015) A co-culture system with an organotypic lung slice and an immortal alveolar macrophage cell line to quantify silica-induced inflammation. PLoS ONE 10:e0117056. https://doi.org/10.1371/journal.pone.0117056
Horvath L, Umehara Y, Jud C, Blank F, Petri-Fink A, Rothen-Rutishauser B (2015) Engineering an in vitro air-blood barrier by 3D bioprinting. Scientific Reports 5:7974. https://doi.org/10.1038/srep07974
Horvath P et al (2016) Screening out irrelevant cell-based models of disease. Nat Rev Drug Discov 15:751–769. https://doi.org/10.1038/nrd.2016.175
Hsu T-H, Xiao J-L, Tsao Y-W, Kao Y-L, Huang S-H, Liao W-Y, Lee C-H (2011) Analysis of the paracrine loop between cancer cells and fibroblasts using a microfluidic chip. Lab Chip 11:1808–1814. https://doi.org/10.1039/C1LC20090A
Huber JM et al (2016) Evaluation of assays for drug efficacy in a three-dimensional model of the lung. J Cancer Res Clin Oncol 142:1955–1966. https://doi.org/10.1007/s00432-016-2198-0
Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE (2010) Reconstituting organ-level lung functions on a chip. Science 328:1662–1668. https://doi.org/10.1126/science.1188302
Huh D et al (2012) A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci Transl Med 4:159ra147. https://doi.org/10.1126/scitranslmed.3004249
Jacquet M, Lambert V, Todaro A, Kremers P (1997) Mitogen-activated lymphocytes: a good model for characterising lung CYP1A1 inducibility. Eur J Epidemiol 13:177–183. https://doi.org/10.1023/a:1007354532547
Jin Woo L et al (2016) Development of a 3D cell printed construct considering angiogenesis for liver tissue engineering. Biofabrication 8:015007
Jung J (2014) Human tumor xenograft models for preclinical assessment of anticancer drug development. Toxicol Res 30:1–5. https://doi.org/10.5487/tr.2014.30.1.001
Karekla E et al (2017) Ex vivo explant cultures of non-small cell lung carcinoma enable evaluation of primary tumor responses to anticancer therapy. Cancer Res 77:2029–2039. https://doi.org/10.1158/0008-5472.can-16-1121
Kellar A, Egan C, Morris D (2015) Preclinical murine models for lung cancer: clinical trial applications. Biomed Res Int 2015:621324. https://doi.org/10.1155/2015/621324
Kim HJ et al (2015) Airway Smooth muscle sensitivity to methacholine in precision-cut lung slices (PCLS) from ovalbumin-induced asthmatic mice korean. J Physiol Pharmacol 19:65–71. https://doi.org/10.4196/kjpp.2015.19.1.65
Kistemaker LE et al (2017) The PDE4 inhibitor CHF-6001 and LAMAs inhibit bronchoconstriction-induced remodelling in lung slices. Am J Physiol Lung Cell Mol Physiol: ajplung 00069 02017. https://doi.org/10.1152/ajplung.00069.2017
Konishi S et al (2016) Directed induction of functional multi-ciliated cells in proximal airway epithelial spheroids from human pluripotent stem cells. Stem Cell Reports 6:18–25. https://doi.org/10.1016/j.stemcr.2015.11.010
Koziol-White CJ et al (2016a) Inhibition of spleen tyrosine kinase attenuates IgE-mediated airway contraction and mediator release in human precision cut lung slices. Br J Pharmacol 173:3080–3087. https://doi.org/10.1111/bph.13550
Koziol-White CJ et al (2016b) Inhibition of PI3 K promotes dilation of human small airways in a rho kinase-dependent manner. Br J Pharmacol 173:2726–2738. https://doi.org/10.1111/bph.13542
Kumar PA et al (2011) Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection. Cell 147:525–538. https://doi.org/10.1016/j.cell.2011.10.001
Lama R, Zhang L, Naim JM, Williams J, Zhou A, Su B (2013) Development, validation and pilot screening of an in vitro multi-cellular three-dimensional cancer spheroid assay for anti-cancer drug testing. Bioorg Med Chem 21:922–931. https://doi.org/10.1016/j.bmc.2012.12.007
Lauenstein L et al (2014) Assessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS). Toxicol In Vitro 28:588–599. https://doi.org/10.1016/j.tiv.2013.12.016
Lenz AG et al (2014) Efficient bioactive delivery of aerosolized drugs to human pulmonary epithelial cells cultured in air-liquid interface conditions. Am J Respir Cell Mol Biol 51:526–535. https://doi.org/10.1165/rcmb.2013-0479OC
Leung AWY et al (2017) In vivo validation of PAPSS1 (3’-phosphoadenosine 5’-phosphosulfate synthase 1) as a Cisplatin-Sensitizing Therapeutic Target. Clin Cancer Res. https://doi.org/10.1158/1078-0432.ccr-17-0700
Martin C, Uhlig S, Ullrich V (2001) Cytokine-induced bronchoconstriction in precision-cut lung slices is dependent upon cyclooxygenase-2 and thromboxane receptor activation. Am J Respir Cell Mol Biol 24:139–145. https://doi.org/10.1165/ajrcmb.24.2.3545
Mas C, Boda B, CaulFuty M, Huang S, Wiszniewski L, Constant S (2015) Antitumour efficacy of the selumetinib and trametinib MEK inhibitors in a combined human airway-tumour-stroma lung cancer model. J Biotechnol 205:111–119. https://doi.org/10.1016/j.jbiotec.2015.01.012
Mathis C et al (2013) Human bronchial epithelial cells exposed in vitro to cigarette smoke at the air-liquid interface resemble bronchial epithelium from human smokers. Am J Physiol Lung Cell Mol Physiol 304:L489–L503. https://doi.org/10.1152/ajplung.00181.2012
Meenach SA, Tsoras AN, McGarry RC, Mansour HM, Hilt JZ, Anderson KW (2016) Development of three-dimensional lung multicellular spheroids in air- and liquid-interface culture for the evaluation of anticancer therapeutics. Int J Oncol 48:1701–1709. https://doi.org/10.3892/ijo.2016.3376
Morgan MM, Johnson BP, Livingston MK, Schuler LA, Alarid ET, Sung KE, Beebe DJ (2016) Personalized in vitro cancer models to predict therapeutic response: challenges and a framework for improvement. Pharmacol Ther 165:79–92. https://doi.org/10.1016/j.pharmthera.2016.05.007
Morgan KM, Riedlinger GM, Rosenfeld J, Ganesan S, Pine SR (2017) Patient-Derived Xenograft Models of Non-Small Cell Lung Cancer and Their Potential Utility in Personalized Medicine. Front Oncol 7:2. https://doi.org/10.3389/fonc.2017.00002
Morin JP, Baste JM, Gay A, Crochemore C, Corbiere C, Monteil C (2013) Precision cut lung slices as an efficient tool for in vitro lung physio-pharmacotoxicology studies. Xenobiotica 43:63–72. https://doi.org/10.3109/00498254.2012.727043
Muller-Redetzky HC et al (2012) Intermedin stabilized endothelial barrier function and attenuated ventilator-induced lung injury in mice. PLoS ONE 7:e35832. https://doi.org/10.1371/journal.pone.0035832
Munoz-Abraham AS, Rodriguez-Davalos MI, Bertacco A, Wengerter B, Geibel JP, Mulligan DC (2016) 3D printing of organs for transplantation: where are we and where are we heading? Curr Transplant R 3:93–99. https://doi.org/10.1007/s40472-016-0089-6
Murphy SV, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32:773–785. https://doi.org/10.1038/nbt.2958
Nagarsheth N, Wicha MS, Zou W (2017) Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol 17:559–572. https://doi.org/10.1038/nri.2017.49
Neuhaus V et al (2013) Functional testing of an inhalable nanoparticle based influenza vaccine using a human precision cut lung slice technique. PLoS ONE 8:e71728. https://doi.org/10.1371/journal.pone.0071728
Neuhaus V et al (2017) Assessment of long-term cultivated human precision-cut lung slices as an ex vivo system for evaluation of chronic cytotoxicity and functionality. J Occup Med Toxicol 12:13. https://doi.org/10.1186/s12995-017-0158-5
Nikolić MZ, Rawlins EL (2017) Lung organoids and their use to study cell-cell interaction. Curr Pathobiol Rep 5:223–231. https://doi.org/10.1007/s40139-017-0137-7
Onion D et al (2016) 3-dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors. Mol Cancer Ther 15:753–763. https://doi.org/10.1158/1535-7163.mct-15-0598
Pezzulo AA et al (2011) The air-liquid interface and use of primary cell cultures are important to recapitulate the transcriptional profile of in vivo airway epithelia. Am J Physiol Lung Cell Mol Physiol 300:L25–L31. https://doi.org/10.1152/ajplung.00256.2010
Pisanu ME et al (2017) Blockade of Stearoyl-CoA-desaturase 1 activity reverts resistance to cisplatin in lung cancer stem cells. Cancer Lett 406:93–104. https://doi.org/10.1016/j.canlet.2017.07.027
Pomerenke A, Lea SR, Herrick S, Lindsay MA, Singh D (2016) Characterization of TLR-induced inflammatory responses in COPD and control lung tissue explants. Int J Chron Obstruct Pulmon Dis 11:2409–2417. https://doi.org/10.2147/copd.s105156
Popper H (2017a) Lung tumors. In: Pathology of lung disease: morphology—pathogenesis—etiology. Springer, Berlin, pp 353–575. https://doi.org/10.1007/978-3-662-50491-8_17
Popper H (2017b) Normal lung. In: Pathology of lung disease: morphology—pathogenesis—etiology. Springer Berlin, pp 7–20. https://doi.org/10.1007/978-3-662-50491-8_2
Razian G, Yu Y, Ungrin M (2013) Production of large numbers of size-controlled tumor spheroids using microwell plates. J Visualized Exp: JoVE:50665. https://doi.org/10.3791/50665
Ressmeyer AR, Larsson AK, Vollmer E, Dahlen SE, Uhlig S, Martin C (2006) Characterisation of guinea pig precision-cut lung slices: comparison with human tissues. Eur Respir J 28:603–611. https://doi.org/10.1183/09031936.06.00004206
Rieg AD et al (2014) Milrinone relaxes pulmonary veins in guinea pigs and humans. PLoS ONE 9:e87685. https://doi.org/10.1371/journal.pone.0087685
Rimington TL et al (2017) Defining the inflammatory signature of human lung explant tissue in the presence and absence of glucocorticoid. F1000Res 6:460. https://doi.org/10.12688/f1000research.10961.1
Rock JR, Gao X, Xue Y, Randell SH, Kong Y-Y, Hogan BLM (2011) Notch-dependent differentiation of adult airway basal stem cells. Cell Stem Cell 8:639–648. https://doi.org/10.1016/j.stem.2011.04.003
Russo MV et al (2015) A new mouse avatar model of non-small cell lung cancer Front. Oncol 5:52. https://doi.org/10.3389/fonc.2015.00052
Salar-Behzadi S, Wu S, Mercuri A, Meindl C, Stranzinger S, Frohlich E (2017) Effect of the pulmonary deposition and in vitro permeability on the prediction of plasma levels of inhaled budesonide formulation. Int J Pharm 532:337–344. https://doi.org/10.1016/j.ijpharm.2017.08.124
Sato M et al (2006) Multiple oncogenic changes (K-RASV12, p53 Knockdown, Mutant EGFRs, p16 Bypass, Telomerase) are not sufficient to confer a full malignant phenotype on human bronchial epithelial cells. Can Res 66:2116–2128. https://doi.org/10.1158/0008-5472.can-05-2521
Schamberger AC, Staab-Weijnitz CA, Mise-Racek N, Eickelberg O (2015) Cigarette smoke alters primary human bronchial epithelial cell differentiation at the air-liquid interface. Sci Rep 5:8163. https://doi.org/10.1038/srep08163
Schleputz M et al (2012) Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS). PLoS ONE 7:e47344. https://doi.org/10.1371/journal.pone.0047344
Seehase S et al (2012) LPS-induced lung inflammation in marmoset monkeys—an acute model for anti-inflammatory drug testing. PLoS ONE 7:e43709. https://doi.org/10.1371/journal.pone.0043709
Shamir ER, Ewald AJ (2014) Three-dimensional organotypic culture: experimental models of mammalian biology and disease. Nat Rev Mol Cell Biol 15:647–664. https://doi.org/10.1038/nrm3873
Switalla S et al (2010) Natural innate cytokine response to immunomodulators and adjuvants in human precision-cut lung slices. Toxicol Appl Pharmacol 246:107–115. https://doi.org/10.1016/j.taap.2010.04.010
Temann A, Golovina T, Neuhaus V, Thompson C, Chichester JA, Braun A, Yusibov V (2017) Evaluation of inflammatory and immune responses in long-term cultured human precision-cut lung slices. Hum Vaccin Immunother 13:351–358. https://doi.org/10.1080/21645515.2017.1264794
van den Bosch T et al (2017) A 6-alkylsalicylate histone acetyltransferase inhibitor inhibits histone acetylation and pro-inflammatory gene expression in murine precision-cut lung slices. Pulm Pharmacol Ther 44:88–95. https://doi.org/10.1016/j.pupt.2017.03.006
Van Dijk EM, Culha S, Menzen MH, Bidan CM, Gosens R (2016) Elastase-induced parenchymal disruption and airway hyper responsiveness in mouse precision cut lung slices: toward an ex vivo COPD Model. Front Physiol 7:657. https://doi.org/10.3389/fphys.2016.00657
Vicary GW, Vergne Y, Santiago-Cornier A, Young LR, Roman J (2016) Pulmonary Fibrosis in Hermansky-Pudlak Syndrome. Ann Am Thorac Soc 13:1839–1846. https://doi.org/10.1513/AnnalsATS.201603-186FR
Waypa GB et al (2013) Superoxide generated at mitochondrial complex III triggers acute responses to hypoxia in the pulmonary circulation. Am J Respir Crit Care Med 187:424–432. https://doi.org/10.1164/rccm.201207-1294OC
Weiswald L-B, Bellet D, Dangles-Marie V (2015) Spherical cancer models in tumor biology. Neoplasia 17:1–15. https://doi.org/10.1016/j.neo.2014.12.004
Wijeweera JB, Gandolfi AJ, Parrish A, Lantz RC (2001) Sodium arsenite enhances AP-1 and NFkappaB DNA binding and induces stress protein expression in precision-cut rat lung slices. Toxicol Sci 61:283–294
Wohlsen A, Uhlig S, Martin C (2001) Immediate allergic response in small airways. Am J Respir Crit Care Med 163:1462–1469. https://doi.org/10.1164/ajrccm.163.6.2007138
Wohlsen A et al (2003) The early allergic response in small airways of human precision-cut lung slices. Eur Respir J 21:1024–1032
Wright JL et al (2011) Statin reverses smoke-induced pulmonary hypertension and prevents emphysema but not airway remodeling. Am J Respir Crit Care Med 183:50–58. https://doi.org/10.1164/rccm.201003-0399OC
Xu Z et al (2013) Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer Biomaterials 34:4109–4117. https://doi.org/10.1016/j.biomaterials.2013.02.045
Zanoni M et al (2016) 3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained. Scientific Reports 6:19103. https://doi.org/10.1038/srep19103
Acknowledgements
This research was supported [in part] by the Intramural Research Program of the NIH, NIAID.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Pomerenke, A. (2017). Organotypic Models of Lung Cancer. In: Bagnoli, F., Rappuoli, R. (eds) Three Dimensional Human Organotypic Models for Biomedical Research. Current Topics in Microbiology and Immunology, vol 430. Springer, Cham. https://doi.org/10.1007/82_2017_79
Download citation
DOI: https://doi.org/10.1007/82_2017_79
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-62451-4
Online ISBN: 978-3-030-62452-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)