Encyclopedia of Molecular Pharmacology

Living Edition
| Editors: Stefan Offermanns, Walter Rosenthal

Extracellular Matrix (ECM)

  • Michael Papanicolaou
  • Thomas R. CoxEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-030-21573-6_5691-1
  • 16 Downloads

Definition

The extracellular matrix (ECM) is a dynamic complex of interwoven fibrils and globular macromolecules, coming together to form the foundation of all biological tissue. Comprising of collagens, glycoproteins, and proteoglycans, as well as associated secreted factors and enzymatic regulators, this supramolecular assembly provides structural support for organs and surrounding cellular compartments and also exerts a great degree of extrinsic regulation over cellular phenotype and function. The ECM establishes the extracellular milieu in which cells exist, providing cells with context-specific cues that vary from tissue to tissue, spatially guiding cellular fate, fine-tuning developmental programs, and maintaining tissue order. Such cues are responsible for switching on and off intracellular signaling programs and establishing spatially distinct cellular phenotypes. In disease, genetic aberrations, or the loss of regulation of ECM homeostasis, are observed, leading to deviations...

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References

  1. Chang J et al (2017) Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer. Oncotarget 8:26066–26078.  https://doi.org/10.18632/oncotarget.15257CrossRefPubMedPubMedCentralGoogle Scholar
  2. Filipe EC, Chitty JL, Cox TR (2018) Charting the unexplored extracellular matrix in cancer. Int J Exp Pathol 99:58–76.  https://doi.org/10.1111/iep.12269CrossRefPubMedPubMedCentralGoogle Scholar
  3. Frantz C, Stewart KM, Weaver VM (2010) The extracellular matrix at a glance. J Cell Sci 123:4195–4200.  https://doi.org/10.1242/jcs.023820CrossRefPubMedPubMedCentralGoogle Scholar
  4. Gialeli C, Theocharis AD, Karamanos NK (2011) Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J 278:16–27.  https://doi.org/10.1111/j.1742-4658.2010.07919.xCrossRefPubMedGoogle Scholar
  5. Hamidi H, Ivaska J (2018) Every step of the way: integrins in cancer progression and metastasis. Nat Rev Cancer 18:533–548.  https://doi.org/10.1038/s41568-018-0038-zCrossRefPubMedPubMedCentralGoogle Scholar
  6. Hannezo E, Heisenberg C-P (2019) Mechanochemical feedback loops in development and disease. Cell 178:12–25.  https://doi.org/10.1016/j.cell.2019.05.052CrossRefPubMedGoogle Scholar
  7. Hastings JF, Skhinas JN, Fey D, Croucher DR, Cox TR (2019) The extracellular matrix as a key regulator of intracellular signalling networks. Br J Pharmacol 176:82–92.  https://doi.org/10.1111/bph.14195CrossRefPubMedGoogle Scholar
  8. He Y, Huang C, Lin X, Li J (2013) MicroRNA-29 family, a crucial therapeutic target for fibrosis diseases. Biochimie 95:1355–1359.  https://doi.org/10.1016/j.biochi.2013.03.010CrossRefPubMedGoogle Scholar
  9. Hingorani SR et al (2018) HALO 202: randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine versus nab-paclitaxel/gemcitabine in patients with untreated, metastatic pancreatic ductal adenocarcinoma. J Clin Oncol 36:359–366.  https://doi.org/10.1200/JCO.2017.74.9564CrossRefPubMedGoogle Scholar
  10. Hirsch T et al (2017) Regeneration of the entire human epidermis using transgenic stem cells. Nature 551:327–332.  https://doi.org/10.1038/nature24487CrossRefPubMedPubMedCentralGoogle Scholar
  11. Isaka Y et al (1996) Gene therapy by skeletal muscle expression of decorin prevents fibrotic disease in rat kidney. Nat Med 2:418–423.  https://doi.org/10.1038/nm0496-418CrossRefPubMedGoogle Scholar
  12. Jarvelainen H, Sainio A, Koulu M, Wight TN, Penttinen R (2009) Extracellular matrix molecules: potential targets in pharmacotherapy. Pharmacol Rev 61:198–223.  https://doi.org/10.1124/pr.109.001289CrossRefPubMedPubMedCentralGoogle Scholar
  13. Katz LH et al (2013) Targeting TGF-beta signaling in cancer. Expert Opin Ther Targets 17:743–760.  https://doi.org/10.1517/14728222.2013.782287CrossRefPubMedPubMedCentralGoogle Scholar
  14. Leung L et al (2019) Anti-metastatic inhibitors of Lysyl oxidase (LOX): design and structure–activity relationships. J Med Chem 62:5863–5884.  https://doi.org/10.1021/acs.jmedchem.9b00335CrossRefPubMedPubMedCentralGoogle Scholar
  15. Ley K, Rivera-Nieves J, Sandborn WJ, Shattil S (2016) Integrin-based therapeutics: biological basis, clinical use and new drugs. Nat Rev Drug Discov 15:173–183.  https://doi.org/10.1038/nrd.2015.10CrossRefPubMedPubMedCentralGoogle Scholar
  16. Lu P, Takai K, Weaver VM, Werb Z (2011) Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol 3.  https://doi.org/10.1101/cshperspect.a005058CrossRefGoogle Scholar
  17. Midwood KS, Williams LV, Schwarzbauer JE (2004) Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol 36:1031–1037.  https://doi.org/10.1016/j.biocel.2003.12.003CrossRefPubMedGoogle Scholar
  18. Mouw JK, Ou G, Weaver VM (2014) Extracellular matrix assembly: a multiscale deconstruction. Nat Rev Mol Cell Biol 15:771–785.  https://doi.org/10.1038/nrm3902CrossRefPubMedPubMedCentralGoogle Scholar
  19. Naba A et al (2012) The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol Cell Proteomics 11:M111.014647.  https://doi.org/10.1074/mcp.M111.014647CrossRefPubMedGoogle Scholar
  20. Nelson CM, Bissell MJ (2005) Modeling dynamic reciprocity: engineering three-dimensional culture models of breast architecture, function, and neoplastic transformation. Semin Cancer Biol 15:342–352.  https://doi.org/10.1016/j.semcancer.2005.05.001CrossRefPubMedPubMedCentralGoogle Scholar
  21. Nelson CM, Bissell MJ (2006) Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. Annu Rev Cell Dev Biol 22:287–309.  https://doi.org/10.1146/annurev.cellbio.22.010305.104315CrossRefPubMedPubMedCentralGoogle Scholar
  22. Noetel A, Kwiecinski M, Elfimova N, Huang J, Odenthal M (2012) microRNA are central players in anti- and profibrotic gene regulation during liver fibrosis. Front Physiol 3:49.  https://doi.org/10.3389/fphys.2012.00049CrossRefPubMedPubMedCentralGoogle Scholar
  23. Perrin A, Rousseau J, Tremblay JP (2017) Increased expression of laminin subunit alpha 1 chain by dCas9-VP160. Mol Ther Nucleic Acids 6:68–79.  https://doi.org/10.1016/j.omtn.2016.11.004CrossRefPubMedGoogle Scholar
  24. Piperigkou Z, Karamanos NK (2019) Dynamic interplay between miRNAs and the extracellular matrix influences the tumor microenvironment. Trends Biochem Sci.  https://doi.org/10.1016/j.tibs.2019.06.007CrossRefGoogle Scholar
  25. Pozzi A, Yurchenco PD, Iozzo RV (2017) The nature and biology of basement membranes. Matrix Biol 57–58:1–11.  https://doi.org/10.1016/j.matbio.2016.12.009CrossRefPubMedGoogle Scholar
  26. Rath N et al (2017) ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth. EMBO Mol Med 9:198–218.  https://doi.org/10.15252/emmm.201606743CrossRefPubMedGoogle Scholar
  27. Schuppan D, Ashfaq-Khan M, Yang AT, Kim YO (2018) Liver fibrosis: direct antifibrotic agents and targeted therapies. Matrix Biol 68-69:435–451.  https://doi.org/10.1016/j.matbio.2018.04.006CrossRefPubMedGoogle Scholar
  28. Trackman PC (2016) Lysyl oxidase isoforms and potential therapeutic opportunities for fibrosis and cancer. Expert Opin Ther Targets 20:935–945.  https://doi.org/10.1517/14728222.2016.1151003CrossRefPubMedPubMedCentralGoogle Scholar
  29. Vennin C et al (2017) Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Sci Transl Med 9.  https://doi.org/10.1126/scitranslmed.aai8504CrossRefGoogle Scholar
  30. Wynn TA (2008) Cellular and molecular mechanisms of fibrosis. J Pathol 214:199–210.  https://doi.org/10.1002/path.2277CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg New York 2020

Authors and Affiliations

  1. 1.The Kinghorn Cancer CentreGarvan Institute of Medical ResearchSydneyAustralia
  2. 2.School of Life SciencesUniversity of Technology SydneySydneyAustralia
  3. 3.St. Vincent’s Clinical School, Faculty of MedicineUNSW SydneySydneyAustralia