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Decellularized normal and cancer tissues as tools for cancer research

Cancer Gene Therapy volume 29, pages 879–888 (2022)Cite this article

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Abstract

Today it is widely accepted that molecular mechanisms triggering cancer initiate with a genetic modification. However, a genetic alteration providing the aberrant clone with a growing advantage over neighboring cells is not sufficient to develop cancer. Currently, tumors are considered a heterogeneous population of cells and an extracellular matrix (ECM) that make up a characteristic microenvironment. Interactions between tumor cells and cancer microenvironment define cancer progression and therapeutic response. To investigate and clarify the role of ECM in the regulation of cancer cell behavior and response to therapy, the decellularization of ECM, a widely used technique in tissue engineering, has been recently employed to develop 3D culture model of disease. In this review, we briefly explore the different components of healthy and pathological ECM and the methods to obtain and characterize the ECM from native bioptic tissue. Finally, we highlight the most relevant applications of ECM in translational cancer research strategies: decellularized ECM, ECM-hydrogel and 3D bioprinting.

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Fig. 1: Decellularized ECM from processing to applications.

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References

  1. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: cancer today. Lyon: International Agency for Research on Cancer; 2020 (https://gco.iarc.fr/today, accessed February 2021).

  2. Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010;123:4195–4200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK. Extracellular matrix structure. Adv Drug Deliv Rev. 2016;97:4–27.

    Article  CAS  PubMed  Google Scholar 

  4. Kular JK, Basu S, Sharma RI. The extracellular matrix: structure, composition, age-related differences, tools for analysis and applications for tissue engineering. J Tissue Eng. 2014;5:2041731414557112.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 1953;6:963–968.

    Article  CAS  PubMed  Google Scholar 

  6. Ge L, Meng W, Zhou H, Bhowmick N. Could stroma contribute to field cancerization? Med Hypotheses. 2010;75:26–31.

    Article  PubMed  Google Scholar 

  7. Bissell MJ, Hines WC. Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med. 2011;17:320–329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cox TR, Erler JT. Molecular pathways: connecting fibrosis and solid tumor metastasis staff planners’ disclosures acknowledgment of financial or other support. Clin Cancer Res. 2014;20:3637–3640.

    Article  CAS  PubMed  Google Scholar 

  9. Piersma B, Hayward MK, Weaver VM. Fibrosis and cancer: a strained relationship. Biochim Biophys Acta Rev Cancer. 2020;1873:188356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014;15:786–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sensi F, D’Angelo E, D’Aronco S, Molinaro R, Agostini M. Preclinical three-dimensional colorectal cancer model: The next generation of in vitro drug efficacy evaluation. J Cell Physiol. 2018;34:181–191.

    Google Scholar 

  12. Mendibil U, Ruiz-Hernandez R, Retegi-Carrion S, Garcia-Urquia N, Olalde-Graells B, Abarrategi A. Tissue-specific decellularization methods: rationale and strategies to achieve regenerative compounds. Int J Mol Sci. 2020;21:5447.

    Article  PubMed Central  Google Scholar 

  13. Gilpin A, Yang Y. Decellularization strategies for regenerative medicine: from processing techniques to applications. Biomed Res Int. 2017;2017:9831534.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Kabirian F, Mozafari M. Decellularized ECM-derived bioinks: prospects for the future. Methods 2020;171:108–118.

    Article  CAS  PubMed  Google Scholar 

  15. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials. 2011;32:3233–3243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Huleihel L, Hussey GS, Naranjo JD, Zhang L, Dziki JL, Turner NJ, et al. Matrix-bound nanovesicles within ECM bioscaffolds. Sci Adv. 2016;2:e1600502.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Ali M, Pr AK, Yoo JJ, Zahran F, Atala A, Lee SJ. A photo-crosslinkable kidney ECM-derived bioink accelerates renal tissue formation. Adv Health Mater. 2019;8:e1800992.

    Article  CAS  Google Scholar 

  18. Yao Q, Zheng Y, Lan Q, Kou L, Xu H, Zhao Y. Recent development and biomedical applications of decellularized extracellular matrix biomaterials. Mater Sci Eng C. 2019;104:109942.

    Article  CAS  Google Scholar 

  19. Langer R, Vacanti JP. Tissue engineering. Science. 1993;260:920–926.

    Article  CAS  PubMed  Google Scholar 

  20. Mase VJJ, Hsu JR, Wolf SE, Wenke JC, Baer DG, Owens J, et al. Clinical application of an acellular biologic scaffold for surgical repair of a large, traumatic quadriceps femoris muscle defect. Orthopedics. 2010;33:511.

    Article  PubMed  Google Scholar 

  21. Kochupura PV, Azeloglu EU, Kelly DJ, Doronin SV, Badylak SF, Krukenkamp IB, et al. Tissue-engineered myocardial patch derived from extracellular matrix provides regional mechanical function. Circulation. 2005;112:I144–I149.

    Article  PubMed  Google Scholar 

  22. Badylak SF. The extracellular matrix as a biologic scaffold material. Biomaterials. 2007;28:3587–3593.

    Article  CAS  PubMed  Google Scholar 

  23. Badylak SF, Hoppo T, Nieponice A, Gilbert TW, Davison JM, Jobe BA. Esophageal preservation in five male patients after endoscopic inner-layer circumferential resection in the setting of superficial cancer: a regenerative medicine approach with a biologic scaffold. Tissue Eng A. 2011;17:1643–1650.

    Article  CAS  Google Scholar 

  24. Salzberg CA. Nonexpansive immediate breast reconstruction using human acellular tissue matrix graft (AlloDerm). Ann Plast Surg. 2006;57:1–5.

    Article  CAS  PubMed  Google Scholar 

  25. Liao J, Xu B, Zhang R, Fan Y, Xie H, Li X. Applications of decellularized materials in tissue engineering: advantages, drawbacks and current improvements, and future perspectives. J Mater Chem B. 2020;8:10023–10049.

    Article  CAS  PubMed  Google Scholar 

  26. Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 2012;21:309–322.

    Article  CAS  PubMed  Google Scholar 

  27. Naba A, Clauser KR, Hoersch S, Liu H, Carr SA, Hynes RO. The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol Cell Proteom. 2012;11:M111.014647.

    Article  CAS  Google Scholar 

  28. Cox TR. The matrix in cancer. Nat Rev Cancer. 2021;21:217–238.

    Article  CAS  PubMed  Google Scholar 

  29. Mishra DK, Thrall MJ, Baird BN, Ott HC, Blackmon SH, Kurie JM, et al. Human lung cancer cells grown on acellular rat lung matrix create perfusable tumor nodules. Ann Thorac Surg. 2012;93:1075–1081.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chen HJ, Wei Z, Sun J, Bhattacharya A, Savage DJ, Serda R, et al. A recellularized human colon model identifies cancer driver genes. Nat Biotechnol 2016;34:845–851.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Dunne LW, Huang Z, Meng W, Fan X, Zhang N, Zhang Q, et al. Human decellularized adipose tissue scaffold as a model for breast cancer cell growth and drug treatments. Biomaterials 2014;35:4940–4949.

    Article  CAS  PubMed  Google Scholar 

  32. Piccoli M, D’Angelo E, Crotti S, Sensi F, Urbani L, Maghin E, et al. Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research. J Cell Physiol. 2018;233:5937–5948.

    Article  CAS  PubMed  Google Scholar 

  33. Koh I, Cha J, Park J, Choi J, Kang SG, Kim P. The mode and dynamics of glioblastoma cell invasion into a decellularized tissue-derived extracellular matrix-based three-dimensional tumor model. Sci Rep. 2018;8:4608.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. D’Angelo E, Natarajan D, Sensi F, Ajayi O, Fassan M, Mammano E, et al. Patient-derived scaffolds of colorectal cancer metastases as an organotypic 3D model of the liver metastatic microenvironment. Cancers. 2020;12:364.

    Article  PubMed Central  CAS  Google Scholar 

  35. Saldin LT, Cramer MC, Velankar SS, White LJ, Badylak SF. Extracellular matrix hydrogels from decellularized tissues: Structure and function. Acta Biomaterialia 2017;49:1–15.

    Article  CAS  PubMed  Google Scholar 

  36. Saheli M, Sepantafar M, Pournasr B, Farzaneh Z, Vosough M, Piryaei A, et al. Three-dimensional liver-derived extracellular matrix hydrogel promotes liver organoids function. J Cell Biochem. 2018;119:4320–4333.

    Article  CAS  PubMed  Google Scholar 

  37. Romero-López M, Trinh AL, Sobrino A, Hatch MMS, Keating MT, Fimbres C, et al. Recapitulating the human tumor microenvironment: colon tumor-derived extracellular matrix promotes angiogenesis and tumor cell growth. Biomaterials. 2017;116:118–129.

    Article  PubMed  CAS  Google Scholar 

  38. Jung M, Han Y, Woo C, Ki CS. Pulmonary tissue-mimetic hydrogel niches for small cell lung cancer cell culture. J Mater Chem B. 2021;9:1858–1866.

    Article  CAS  PubMed  Google Scholar 

  39. Hwang J, Sullivan MO, Kiick KL. Targeted drug delivery via the use of ECM-mimetic materials. Front Bioeng Biotechnol. 2020;8:69.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Merino S, Martín C, Kostarelos K, Prato M, Vázquez E. Nanocomposite hydrogels: 3D polymer-nanoparticle synergies for on-demand drug delivery. ACS Nano. 2015;9:4686–4697.

    Article  CAS  PubMed  Google Scholar 

  41. Dimatteo R, Darling NJ, Segura T. In situ forming injectable hydrogels for drug delivery and wound repair. Adv Drug Deliv Rev. 2018;127:167–184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kim J, Jang J, Cho DW. Controlling cancer cell behavior by improving the stiffness of gastric tissue-decellularized ECM bioink with cellulose nanoparticles. Front Bioeng Biotechnol. 2021;9:605819.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Mollica PA, Booth-Creech EN, Reid JA, Zamponi M, Sullivan SM, Palmer XL, et al. 3D bioprinted mammary organoids and tumoroids in human mammary derived ECM hydrogels. Acta Biomater. 2019;95:201–213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Knowlton S, Onal S, Yu CH, Zhao JJ, Tasoglu S. Bioprinting for cancer research. Trends Biotechnol. 2015;33:504–513.

    Article  CAS  PubMed  Google Scholar 

  45. Ma X, Yu C, Wang P, Xu W, Wan X, Lai CSE, et al. Rapid 3D bioprinting of decellularized extracellular matrix with regionally varied mechanical properties and biomimetic microarchitecture. Biomaterials. 2018;185:310–321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yi HG, Jeong YH, Kim Y, Choi YJ, Moon HE, Park SH, et al. A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy. Nat Biomed Eng. 2019;3:509–519.x.

    Article  CAS  PubMed  Google Scholar 

  47. Sato T, Stange DE, Ferrante M, Vries RG. Van Es JH, Van den Brink S, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology. 2011;141:1762–1772.

    Article  CAS  PubMed  Google Scholar 

  48. Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, et al. Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014;159:176–187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Tiriac H, Belleau P, Engle DD, Plenker D, Deschênes A, Somerville TDD, et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov. 2018;8:1112–1129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Seino T, Kawasaki S, Shimokawa M, Tamagawa H, Toshimitsu K, Fujii M, et al. Human pancreatic tumor organoids reveal loss of stem cell niche factor dependence during disease progression. Cell Stem Cell. 2018;22:454–467.e6.

    Article  CAS  PubMed  Google Scholar 

  51. Boj SF, Hwang CI, Baker LA, Chio II, Engle DD, Corbo V, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 2015;160:324–338.

    Article  CAS  PubMed  Google Scholar 

  52. Fujii M, Shimokawa M, Date S, Takano A, Matano M, Nanki K, et al. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell. 2016;18:827–838.

    Article  CAS  PubMed  Google Scholar 

  53. van de Wetering M, Francies HE, Francis JM, Bounova G, Iorio F, Pronk A, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell. 2015;161:933–945.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Kopper O, de Witte CJ, Lõhmussaar K, Valle-Inclan JE, Hami N, Kester L, et al. An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity. Nat Med. 2019;25:838–849.

    Article  CAS  PubMed  Google Scholar 

  55. Hill SJ, Decker B, Roberts EA, Horowitz NS, Muto MG, Worley MJ Jr, et al. Prediction of DNA repair inhibitor response in short-term patient-derived ovarian cancer organoids. Cancer Discov. 2018;8:1404–1421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lee SH, Hu W, Matulay JT, Silva MV, Owczarek TB, Kim K, et al. Tumor evolution and drug response in patient-derived organoid models of bladder. Cancer Cell 2018;173:515–528.e17.

    CAS  Google Scholar 

  57. Broutier L, Mastrogiovanni G, Verstegen MM, Francies HE, Gavarró LM, Bradshaw CR, et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med. 2017;23:1424–1435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kim M, Mun H, Sung CO, Cho EJ, Jeon HJ, Chun SM, et al. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat Commun. 2019;10:3991.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Sachs N, Papaspyropoulos A, Zomer-van Ommen DD, Heo I, Böttinger L, Klay D, et al. Long-term expanding human airway organoids for disease modeling. EMBO J. 2019;38:e100300.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Li X, Francies HE, Secrier M, Perner J, Miremadi A, Galeano-Dalmau N, et al. Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics. Nat Commun. 2018;9:2983.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Boretto M, Maenhoudt N, Luo X, Hennes A, Boeckx B, Bui B, et al. Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening. Nat Cell Biol. 2019;21:1041–1051.

    Article  CAS  PubMed  Google Scholar 

  62. Jacob F, Salinas RD, Zhang DY, Nguyen PTT, Schnoll JG, Wong SZH, et al. A patient-derived glioblastoma organoid model and biobank recapitulates inter- and intra-tumoral heterogeneity. Cell. 2020;180:188–204.e22.

    Article  CAS  PubMed  Google Scholar 

  63. Xiong G, Flynn TJ, Chen J, Trinkle C, Xu R. Development of an ex vivo breast cancer lung colonization model utilizing a decellularized lung matrix. Integr Biol 2015;7:1518–1525.

    Article  CAS  Google Scholar 

  64. Hoshiba T, Tanaka M. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages. Biochem Biophys Res Commun. 2013;439:291–296.

    Article  CAS  PubMed  Google Scholar 

  65. Ferreira LP, Gaspar VM, Mendes L, Duarte IF, Mano JF. Organotypic 3D decellularized matrix tumor spheroids for high-throughput drug screening. Biomaterials. 2021;275:120983.

    Article  CAS  PubMed  Google Scholar 

  66. Jin Q, Liu G, Li S, Yuan H, Yun Z, Zhang W, et al. Decellularized breast matrix as bioactive microenvironment for in vitro three-dimensional cancer culture. J Cell Physiol. 2019;234:3425–3435.

    Article  CAS  PubMed  Google Scholar 

  67. Lv Y, Wang H, Li G, Zhao B. Three-dimensional decellularized tumor extracellular matrices with different stiffness as bioengineered tumor scaffolds. Bioact Mater. 2021;6:2767–2782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Alves SM, Zhu T, Shostak A, Rossen NS, Rafat M. Studying normal tissue radiation effects using extracellular matrix hydrogels. J Vis Exp. 2019;149. https://doi.org/10.3791/59304.

  69. Aguado BA, Caffe JR, Nanavati D, Rao SS, Bushnell GG, Azarin SM, et al. Extracellular matrix mediators of metastatic cell colonization characterized using scaffold mimics of the pre-metastatic niche. Acta Biomater. 2016;33:13–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wishart AL, Conner SJ, Guarin JR, Fatherree JP, Peng Y, McGinn RA, et al. Decellularized extracellular matrix scaffolds identify full-length collagen VI as a driver of breast cancer cell invasion in obesity and metastasis. Sci Adv. 2020;6:eabc3175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hoang VT, Matossian MD, Ucar DA, Elliott S, La J, Wright MK, et al. ERK5 is required for tumor growth and maintenance through regulation of the extracellular matrix in triple negative breast cancer. Front Oncol. 2020;10:1164.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Mazza G, Telese A, Al-Akkad W, Frenguelli L, Levi A, Marrali M, et al. Cirrhotic human liver extracellular matrix 3D scaffolds promote smad-dependent TGF-β1 epithelial mesenchymal transition. Cells. 2019;9:83.

    Article  PubMed Central  CAS  Google Scholar 

  73. Miyauchi Y, Yasuchika K, Fukumitsu K, Ishii T, Ogiso S, Minami T, et al. A novel three-dimensional culture system maintaining the physiological extracellular matrix of fibrotic model livers accelerates progression of hepatocellular carcinoma cells. Sci Rep. 2017;7:9827.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Gaetani R, Aude S, DeMaddalena LL, Strassle H, Dzieciatkowska M, Wortham M, et al. Evaluation of different decellularization protocols on the generation of pancreas-derived hydrogels. Tissue Eng Part C Methods. 2018;24:697–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Tian X, Werner ME, Roche KC, Hanson AD, Foote HP, Yu SK, et al. Organ-specific metastases obtained by culturing colorectal cancer cells on tissue-specific decellularized scaffolds. Nat Biomed Eng. 2018;2:443–452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank Dr. Milvia Chicca for revising the preliminary manuscript and providing suggestions. Figure 1 was designed by Freepik (https://it.freepik.com). This work was supported by the “Department of excellence 2018–2022” initiative of the Italian Ministry of education (MIUR) awarded to the Department of Neuroscience of the University of Padua; Fondazione Cassa di Risparmio di Padova e Rovigo (CARIPARO) Pediatric Research; AIRC Investigator Grant: 19104; Program; LIFELAB Program, Veneto Region; Università degli Studi di Padova, Budget Integrato per la Ricerca dei Dipartimenti: BIRD199592.

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  1. These authors contributed equally: E. Gentilin, E. D’Angelo.

Authors and Affiliations

  1. Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, via G. Orus, 2b, 35129, Padua, Italy

    E. Gentilin & L. Astolfi

  2. LIFELAB Program, Consorzio per la Ricerca Sanitaria-CORIS, Veneto Region, 35128, Padova, Italy

    E. Gentilin, E. D’Angelo, M. Agostini & L. Astolfi

  3. First Surgical Clinic, Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128, Padua, Italy

    E. D’Angelo & M. Agostini

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  1. E. Gentilin
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The conception and design of the study: E.G., E.D. Drafting the article: E.G., E.D. Revising it critically for important intellectual content: L.A., M.A. Final approval of the version to be submitted all.

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Gentilin, E., D’Angelo, E., Agostini, M. et al. Decellularized normal and cancer tissues as tools for cancer research. Cancer Gene Ther 29, 879–888 (2022). https://doi.org/10.1038/s41417-021-00398-2

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