Plasticidade molecular da matriz extracelular contribui para metástase e resistência a terapias / Molecular plasticity of the extracellular matrix contributes to metastasis and resistance to therapies

Authors

  • Aline Elide da Silva Barbosa
  • Jordana Maria Azevedo -Martins
  • Beatriz Aires Lopes
  • Inês Juliana Martorano Giardini
  • Carmen Veríssima Ferreira -Halder

DOI:

https://doi.org/10.34119/bjhrv4n4-250

Keywords:

Matriz Extracelular, Remodelação, Câncer, Metástase, Resistência, Microambiente.

Abstract

A matriz extracelular (MEC) trata-se de um componente não celular presente em todos os tecidos e órgãos e atua não apenas como uma estrutura física importante para os constituintes celulares, mas também como ponto de partida para eventos bioquímicos e biomecânicos essenciais para a morfogênese, diferenciação e homeostase do tecido. A MEC é composta de um conjunto complexo de proteínas fibrosas, proteoglicanos e outras moléculas, tais como citocinas, fatores de crescimento e hormônios, cuja composição varia de tecido para tecido e é alterada frente a diferentes condições fisiológicas (renovação e reparo tecidual) e associadas às doenças, incluindo câncer, razão pela qual componentes da MEC são denominados como Hallmarks do câncer. Neste contexto, a remodelação da MEC é uma das estratégias que os tumores utilizam para criar um microambiente que promove a tumorigênese e metástase através de diferentes mecanismos. Nesta revisão as características funcionais da MEC serão abordadas e também destacado o entendimento atual dos mecanismos físicos, celulares e moleculares pelos quais a MEC do tumor afeta a eficiência da quimioterapia, radioterapia e imunoterapia.

 

 

References

AJETI, V., NADIARNYK, O., PONIK, S. M., KEELY, P. J., ELICEIRI, K. W., et al. (2011). Structural changes in mixed Col I/Col V collagen gels probed by SHG microscopy: implications for probing stromal alterations in human breast cancer. Biomed. Opt. Express., v. 2, n. 8, p. 2307–2316.

ALATRASH, G., JAKHER, H., STAFFORD, P. D., and MITTENDORF, E. A. (2013). Cancer immunotherapies, their safety and toxicity. Expert Opin Drug Saf., v. 12, n. 5, p. 631-645.

ANTONY, J., THIERY, J.P., and HUANG, R.Y-J. (2019). Epithelial-to-mesenchymal transition: lessons from development, insights into cancer and the potential of EMT-subtype based therapeutic intervention. Phys Biol., v. 16, n. 4, p. 041004.

APPELBE, O.K., ZHANG, Q., PELIZZARI, C.A., WEICHSELBAUM, R.R., and KRON, S.J. (2016). Image-guided radiotherapy targets macromolecules through altering the tumor microenvironment. Mol Pharm., v. 13, n. 10, p. 3457–67.

ARTACHO-CORDON, F., RIOS-ARRABAL, S., LARA P. C., ARTACHO-CORDON, A., CALVENTE, I., et al. (2012). Matrix metalloproteinases: potential therapy to prevent the development of second malignancies after breast radiotherapy. Surg. Oncol., v.21, n. 3, p. e143–e151.

BAKER, A. M., BIRD, D., WELTI, J. C., GOURLAOUEN, M., LANG, G., et al. (2013). Lysyl oxidase plays a critical role in endothelial cell stimulation to drive tumor angiogenesis. Cancer Res., v. 73, n. 2, p. 583–594.

BADIGA A. V., CHETTY C., KESANAKURTI D., ARE D., GUJRATI M., et al. (2011). MMP-2 siRNA inhibits radiation-enhanced invasiveness in glioma cells. PLoS ONE, v. 6, n. 6, p. 6:e20614.

BAR, J. K., GRELEWSKI, P., POPIELA, A., NOGA, L., and RABCZYNSKI, J. (2004). Type IV collagen and CD44v6 expression in benign, malignant primary and metastatic ovarian tumors: correlation with Ki-67 and p53 immunoreactivity. Gynecol. Oncol., v. 95, n. 1, p. 23–31.

BARKER, N., HUCH, M., KUJALA, P., VAN DE WETERING, M., SNIPPERT, H.J., et al. (2010). Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell, v. 6, n. 1, p. 25–36.

BARKER, H. E., PAGET, J. T., KHAN, A. A., and HARRINGTON, K. J. (2015). The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nature Reviews Cancer, v. 15, n. 7, p. 409-425.

BARSKY, S. H., RAO, C. N., GROTENDORST, G. R., and LIOTTA, L. A. (1982). Increased content of type V collagen in desmoplasia of human breast carcinoma. Am. J. Pathol., v. 108, n. 3, p. 276–283.

BARSOUM, I. B., HAMILTON T. K., LI X., COTECHINI T., MILES E. A., et al. (2011). Hypoxia induces escape from innate immunity in cancer cells via increased expression of ADAM10: role of nitric oxide. Cancer Res., v. 71, n. 24, p. 7433-41.

BONNANS, C., CHOU, J., and WERB, Z. (2014). Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol., v. 15, n. 12, p. 786–801.

CASEY, T., BOND, J., TIGHE, S., HUNTER, T., LINTAULT, L., et al. (2009). Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer. Breast Cancer Res. Treat., v. 114, n. 1, p. 47–62.

CASTERMANS, K., and GRIFFIOEN A. W. (2007). Tumor blood vessels, a difficult hurdle for infiltrating leukocytes. Biochim. Biophys. Acta, v. 1776, n. 2, p. 160-74.

CONTI, J. A., KENDALL, T. J., BATEMAN, A., ARMSTRONG, T. A., PAPA-ADAMS, A., et al. (2008). The desmoplastic reaction surrounding hepatic colorectal adenocarcinoma metastases aids tumor growth and survival via ?v integrin ligation. Clin. Cancer Res., v. 14, n. 20, p. 6405–6413.

CORDES, N., SEIDLER, J., DURZOK, R., GEINITZ, H., and BRAKEBUSCH, C. (2006). beta1-integrin-mediated signaling essentially contributes to cell survival after radiation-induced genotoxic injury. Oncogene, v. 25, n. 9, p. 1378-90.

COX, T. R., and ERLER, J. T. (2011). Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis. Model Mech., v. 4, n. 2, p. 165–178.

CHENG, J.C., CHOU, C.H., KUO, M.L., and HSIEH, C.Y. (2006). Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappaB signal transduction pathway. Oncogene, v. 25, n. 53, p. 7009–18.

CHETTY, C., BHOOPATHI, P., RAO, J.S., and LAKKA, S.S. (2009). Inhibition of matrix metalloproteinase-2 enhances radiosensitivity by abrogating radiation-induced FoxM1-mediated G2/M arrest in A549 lung cancer cells. Int J Cancer, v. 124, n. 10, p. 2468–77.

CHITADZE, G., LETTAU M., BHAT J., WESCH D., STEINLE A., et al. (2013). Shedding of endogenous MHC class I-related chain molecules A and B from different human tumor entities: heterogeneous involvement of the “a disintegrin and metalloproteases” 10 and 17. Int. J. Cancer, v. 133, n. 7, p. 1557-66.

CHUNG, E.J., HUDAK, K., HORTON, J.A., WHITE, A., SCROGGINS, B.T., et al. (2014). Transforming growth factor alpha is a critical mediator of radiation lung injury. Radiat Res., v. 182, n. 3, p. 350–62.

DERYUGINA, E.I., and QUIGLEY, J.P. (2006). Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev., v. 25, n. 1, p. 9-34.

DARVIN, P., TOOR, S. M., NAIR, V. S., and ELKORD, E. (2018). Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med., v. 50, n. 12, p. 1-11.

DAVIES, C.L., LUNDSTRØM, L.M., FRENGEN, J., EIKENES, L., BRULAND, SØS, et al. (2004). Radiation improves the distribution and uptake of liposomal doxorubicin (caelyx) in human osteosarcoma xenografts. Cancer Res., v. 64, n. 2, p. 547–53.

DEAK, S. B., GLAUG, M. R., PIERCE, R. A., BANCILA, E., AMENTA, P., et al. (1991). Desmoplasia in benign and malignant breast disease is characterized by alterations in level of mRNAs coding for types I and III procollagen. Matrix., v. 11, n. 4, p. 252–258.

DESGROSELLIER, J.S., and CHERESH, D.A. (2010). Integrins in cancer: biological implications and therapeutic opportunities. Nat. Rev. Cancer, v. 10, n. 1, p. 9–22.

DEWHIRST, M. W., and SECOMB, T. W. (2017). Transport of drugs from blood vessels to tumour tissue. Nat. Rev. Cancer, v. 17, n. 12, p. 738–750.

DOUBLIER, S., BELISARIO, D. C., POLIMENI, M., ANNARATONE, L., RIGANTI, C., et al. (2012). HIF-1 activation induces doxorubicin resistance in MCF7 3-D spheroids via P-glycoprotein expression: a potential model of the chemo-resistance of invasive micropapillary carcinoma of the breast. BMC Cancer, v. 12, n. 1, p. 4.

DUDLEY, M. E., and ROSENBERG, S. A. (2003). Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nat Rev Cancer, v. 3, n. 9, p. 666-75.

EGEBLAD, M., and WERB, Z. (2002). New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer., v. 2, n. 3, p. 161–74.

EIKENBERRY, S. (2009). A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors. Theor. Biol. Med. Model., v. 6, n. 1, p. 16.

ESPINOZA, I., and MIELE, L. (2013). Deadly crosstalk: Notch signaling at the intersection of EMT and cancer stem cells. Cancer Lett., v. 341, n. 1, p. 41-5.

FANG, S., DAI, Y., MEI, Y., YANG, M., HU, L., et al. (2019). Clinical significance and biological role of cancer-derived type I collagen in lung and esophageal cancers. Thorac Cancer, v. 10, n. 2, p. 277–288.

FERREIRA, C.V., MILANI, R., ZAMBUZZI, W.F., and CARVALHO, H.F. (2013). Transdução de sinal. In: A Célula. 3. Ed. São Paulo: Manole Ltda., p. 489–500.

FRISCH, S.M., and SCREATON, R.A. (2001). Anoikis mechanisms. Curr Opin Cell Biol., v. 13, n. 5, p. 555-62.

GARCÍA, R., MERINO, D., GÓMEZ, J. M., NISTAL, J. F., HURLÉ, M. A., et al. (2016). Extracellular heat shock protein 90 binding to TGF? receptor I participates in TGF?-mediated collagen production in myocardial fibroblasts. Cell. Signal., v. 28, n. 10, p. 1563–1579.

GRAHAM, K., and UNGER, E. (2018). Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment. Int. J. Nanomedicine, v. 13, n. 1, p. 6049–6058.

GAVALAS, N. G., TSIATAS, M., TSITSILONIS, O., POLITI, E., IOANNOU, K., et al. (2012). VEGF directly suppresses activation of T cells from ascites secondary to ovarian cancer via VEGF receptor type 2. Br. J. Cancer, v. 107, n. 11, p. 1869-75.

GIUSTINI, A.J., PETRYK, A.A., and HOOPES, P.J. (2012). Ionizing radiation increases systemic nanoparticle tumor accumulation. Nanomedicine, v. 8, n. 6, p. 818–21.

GOEL, H.L., SAYEED, A., BREEN, M., ZARIF, M.J., GARLICK, D.S., et al. (2013). ?(1) integrins mediate resistance to ionizing radiation in vivo by inhibiting c-Jun amino terminal kinase 1. J Cell Physiol., v. 228, n. 7, p. 1601–9.

GOTTESMAN, M.M. (2002). Mechanisms of Cancer Drug Resistance. Annual Review of Medicine, v. 53, n. 1, p. 615–627.

GRIFFIOEN, A. W., DAMEN, C. A., BLIJHAM, G. H., and GROENEWEGEN G. (1996). Tumor angiogenesis is accompanied by a decreased inflammatory response of tumor-associated endothelium. Blood, v. 88, n. 2, p. 667–673.

HALL, J. E., FU, W., SCHALLER, M. D. (2011). Focal Adhesion Kinase: Exploring FAK Structure to Gain Insight into Function. Int Rev Cell Mol Biol., v. 288, n. 1, p. 185 - 225.

HALLAHAN, D.E., QU, S., GENG, L., CMELAK, A., CHAKRAVARTHY, A., et al. (2001). Radiation-mediated control of drug delivery. Am J Clin Oncol., v. 24, n. 5, p. 473–80.

HALLMANN, R., ZHANG, X., DI RUSSO, J., LI, L., SONG, J., et al. (2015). The regulation of immune cell trafficking by the extracellular matrix. Curr. Opin. Cell Biol., v. 36, n. 1, p. 54-61.

HAMIDI, H., and IVASKA, J. (2018). Every step of the way: integrins in cancer progression and metastasis. Nat. Rev. Cancer, v. 18, n. 9, p. 533–548.

HANAHAN, D., and WEINBERG, R.A. (2011). Hallmarks of cancer: the next generation. Cell., v. 144, n. 5, p. 646–674.

HASTINGS, J. F., SKHINAS, J. N., FEY, D., CROUCHER, D. R., and COX T. R. (2019). The extracellular matrix as a key regulator of intracellular signalling networks. Br. J. Pharmacol., v. 176, n. 1, p. 82–92.

HODKINSON, P.S., ELLIOTT, T., WONG, W.S., RINTOUL, R.C., MACKINNON, A.C., et al. (2006). ECM overrides DNA damage-induced cell cycle arrest and apoptosis in small-cell lung cancer cells through beta1 integrin-dependent activation of PI3-kinase. Cell Death Differ., v. 13, n. 10, p. 1776–88.

HOFFMANN, W. (2012). Stem cells, self-renewal and cancer of the gastric epithelium. Curr Med Chem., v. 19, n. 35, p. 5975-83.

HOPE, C., EMMERICH, P. B., PAPADAS, A., PAGENKOPF, A., MATKOWSKYJ, K. A., et al. (2017). Versican-derived matrikines regulate Batf3-dendritic cell differentiation and promote T cell infiltration in colorectal cancer. J. Immunol., v. 199, n. 5, p. 1933-1941.

HORSMAN, M. R., AND OVERGAARD, J. (2016). The impact of hypoxia and its modification of the outcome of radiotherapy. J. Radiat. Res. 57(Suppl. 1): i90–i98.

HUMPHREY, J.D., DUFRESNE, E.R., and SCHWARTZ, M.A. (2014). Mechanotransduction and extracellular matrix homeostasis. Nat. Rev. Mol. Cell Biol., v. 15, n. 12, p. 802–812.

ISHIMOTO, T., MIYAKE, K., NANDI, T., YASHIRO, M., ONISHI, N., et al. (2017). Activation of Transforming Growth Factor Beta 1 Signaling in Gastric Cancer-associated Fibroblasts Increases Their Motility, via Expression of Rhomboid 5 Homolog 2, and Ability to Induce Invasiveness of Gastric Cancer Cells. Gastroenterology, v. 153, n. 1, p. 191-204.e16.

ISSA-NUMMER, Y., DARB-ESFAHANI, S., LOIBL, S., KUNZ G., NEKLJUDOVA, V., et al. (2013). Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer–a substudy of the neoadjuvant GeparQuinto trial. PLoS One, v. 8, n. 12, p. e79775.

JACOBETZ, M. A., CHAN, D. S., NEESSE, A., BAPIRO, T. E., COOK, N., et al. (2013). Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut., v. 62, n. 1, p. 112–120.

JAIN, R. K. (2014). Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell, v. 26, n. 5, p. 605–622.

JAYADEV, R., and SHERWOOD, D. R. (2017). Basement membranes. Curr. Biol., v. 27, n. 6, p. R207–R211.

JÚNIOR, A. T. F., SAVAZZINI-REIS, B., DE CARVALHO ZORZANELLI, B. A., SADOVSKY, C. I., and CARLETTI, E. Z. B. (2020). Immunotherapy - a review on the new horizons of cancer-fighting. Revista de Medicina, v. 99, p. 148-155.

KAUPPILA, S., STENBÄCK, F., RISTELI, J., JUKKOLA, A., and RISTELI, L. (1998). Aberrant type I and type III collagen gene expression in human breast cancer in vivo. J. Pathol., v. 186, n. 3, p. 262–268.

LALLI, E., and SASSONE-CORSI, P. (1994). Signal transduction and gene regulation: the nuclear response to cAMP. J Biol Chem., v. 269, n. 26, p. 17359-62.

LEE, B. Y., TIMPSON, P., HORVATH, L. G., and DALY, R. J. (2015). FAK signaling in human cancer as a target for therapeutics. Pharmacol Ther., v. 146, p. 132-149.

LEEDHAM, S.J., BRITTAN, M., PRESTON, S.L., MCDONALD, S.A.C., and WRIGHT, N.A. (2006). The stomach periglandular fibroblast sheath: all present and correct. Gut., v. 55, n. 2, p. 295-6.

LEWIS, C. E., and POLLARD, J. W. (2006). Distinct role of macrophages in different tumor microenvironments. Cancer Res., v. 66, n. 2, p. 605-12.

LI, E., and HRISTOVA, K. (2006). Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. Biochemestry, v. 45, n. 20, p. 6241-6251.

LUCERO, H. A., and KAGAN, H. M. (2006). Lysyl oxidase: an oxidative enzyme and effector of cell function. Cell. Mol. Life Sci., v. 63, n. 19-20, p. 2304–2316.

KALISKI, A., MAGGIORELLA, L., CENGEL, K.A., MATHE, D., ROUFFIAC, V., et al. (2005). Angiogenesis and tumor growth inhibition by a matrix metalloproteinase inhibitor targeting radiation-induced invasion. Mol Cancer Ther., v. 4, n. 11, p. 1717–28.

KALOFONOS, H., ROWLINSON, G., and EPENETOS, A.A. (1990). Enhancement of monoclonal antibody uptake in human colon tumor xenografts following irradiation. Cancer Res., v. 50, n. 1, p. 159–63.

KARAMANOS, N.K., THEOCHARIS, A.D., PIPERIGKOU, Z., MANOU, D., PASSI, A., et al. (2021). A guide to the composition and functions of the extracellular matrix. FEBS J., p. 1-63.

KESSENBROCK, K., PLAKS, V., and WERB, Z. (2010). Matrix Metalloproteinases: regulators of the tumor microenvironment. Cell., v. 141 n. 1, p. 52–67.

KIM, H., CHA J., JANG, M., and KIM, P. (2019). Hyaluronic acid-based extracellular matrix triggers spontaneous M2-like polarity of monocyte/macrophage. Biomater. Sci., v. 7, n. 6, p. 2264-2271.

KOJIMA, Y., ACAR, A., EATON, E.N., MELLODY, K.T., SCHEEL, C., et al. (2010) Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A., v. 107, n. 46, p. 20009–14.

MAEDA, H., NAKAMURA, H., and FANG, J. (2013). The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev., v. 65, n. 1, p. 71–9.

MAMMOTO, T., JIANG, A., JIANG, E., PANIGRAHY, D., KIERAN, M. W., et al. (2013). Role of collagen matrix in tumor angiogenesis and glioblastoma multiforme progression. Am. J. Pathol., v. 183, n. 4, p. 1293–1305.

MANTONI, T.S., LUNARDI, S., AL-ASSAR, O., MASAMUNE, A., and BRUNNER, T.B. (2011). Pancreatic stellate cells radioprotect pancreatic cancer cells through beta1-integrin signaling. Cancer Res., v. 71, n. 10, p. 3453–8.

MARIATHASAN, S., TURLEY S. J., NICKLES, D., CASTIGLIONI A., YUEN, K., et al. (2018). TGF? attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature, v. 554, n. 7693, p. 544-548.

MARTINEZ-ZUBIAURRE, I., CHALMERS, A. J., and HELLEVIK, T. (2018). Radiation-induced transformation of immunoregulatory networks in the tumor stroma. Front Immunol., v. 9, p. 1679.

MARTIN, M., LEFAIX, J., and DELANIAN, S. (2000). TGF-beta1 and radiation fibrosis: a master switch and a specific therapeutic target? Int J Radiat Oncol Biol Phys., v. 47, n. 2, p. 277–90.

MEADS, M.B., GATENBY, R.A., and DALTON, W.S. (2009). Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat. Rev. Cancer, v. 9, n. 9, p. 665–674.

MENON, H., RAMAPRIYAN, R., CUSHMAN, T.R., VERMA, V., KIM, H.H., et al. (2019). Role of Radiation Therapy in Modulation of the Tumor Stroma and Microenvironment. Front Immunol., v. 10, p. 193.

MISKOLCZI, Z., SMITH, M. P., ROWLING, E. J., FERGUSON, J., BARRIUSO, J., et al. (2018). Collagen abundance controls melanoma phenotypes through lineage-specific microenvironment sensing. Oncogene, v. 37, n. 23, p. 3166–3182.

MOELLER, B. J., and DEWHIRST, M. W. (2004). Raising the bar: how HIF-1 helps determine tumor radiosensitivity. Cell Cycle, v. 3, n. 9, p. 1107–1110.

MOORE, K.A., and LEMISCHKA, I.R. (2006). Stem cells and their niches. Science, v. 311, p. 1880-5.

MOUW, J.K., OU, G., and WEAVER, V.M. (2014). Extracellular matrix assembly: a multiscale deconstruction. Nat. Rev. Mol. Cell Biol., v. 15, n. 12, p. 771–785.

MSIRIKALE, J.S., KLEIN, J.L., SCHROEDER, J., and ORDER, S.E. (1987). Radiation enhancement of radiolabelled antibody deposition in tumors. Int J Radiat Oncol Biol Phys., v. 13, n. 12, p. 1839–44.

MUSHTAQ, M. U., PAPADAS, A., PAGENKOPF, A., FLIETNER, E., MORROW, Z., et al. (2018). Tumor matrix remodeling and novel immunotherapies: the promise of matrix-derived immune biomarkers. J. Immunother Cancer, v. 6, n. 1, p. 65.

NABA, A., CLAUSER, K.R., DING, H., CHARLES, A.W., CARR, S.A., et al. (2016). The extracellular matrix: tools and insights for the “omics” era. Matrix Biol., v. 49, p. 10–24.

NABA, A., CLAUSER, K. R., HOERSCH, S., LIU, H., CARR, S. A., et al. (2012). The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol. Cell. Proteomics, v. 11, n. 4, p. M111.014647.

NABET, B. Y., QIU, Y., SHABASON, J.E., WU, T.J., YOON, T., et al. (2017). Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer. Cell., v. 170, n. 2, p. 352-366.

NIETO, M.A., HUANG, R.Y-J., JACKSON, R.A and THIERY, J.P. (2016). EMT: 2016. Cell, v. 166, n. 1, p. 21-45.

NIRMALA, C., JASTI, S.L., SAWAYA, R., KYRITSIS, A.P., KONDURI, S.D., et al. (2000). Effects of radiation on the levels of MMP-2, MMP-9 and TIMP-1 during morphogenic glial-endothelial cell interactions. Int J Cancer, v. 88, n 5, p. 766–71.

PAQUETTE, B., BAPTISTE, C., THERRIAULT, H., ARGUIN, G., PLOUFFE, B., et al. (2007). In vitro irradiation of basement membrane enhances the invasiveness of breast cancer cells. Br. J. Cancer, v. 97, n. 11, p. 1505–1512.

PEI, D., SHU, X., GASSAMA-DIAGNE, A., and THIERY, J.P. (2019). Mesenchymal-epithelial transition in development and reprogramming. Nat Cell Biol., v. 21, n. 1, p. 44-53.

PEI, J., PARK, I.H., RYU, H.H., LI, S.Y., LI, C.H., et al. (2015). Sublethal dose of irradiation enhances invasion of malignant glioma cells through p53-MMP 2 pathway in U87MG mouse brain tumor model. Radiat Oncol., v. 10, p. 164.

PENG, M., MO, Y., WANG, Y., WU, P., ZHANG, Y., et al. (2019). Neoantigen vaccine: an emerging tumor immunotherapy. Mol. Cancer, v. 18, n. 1, p. 128.

PEYROL, S., RACCURT, M., GERARD, F., GLEYZAL, C., GRIMAUD, J. A., et al. (1997). Lysyl oxidase gene expression in the stromal reaction to in situ and invasive ductal breast carcinoma. Am. J. Pathol., v. 150, n. 2, p. 497–507.

PORSCH, H., BERNERT, B., MEHIC, M., THEOCHARIS, A. D., HELDIN, C. H., et al. (2013). Efficient TGF?-induced epithelial–mesenchymal transition depends on hyaluronan synthase HAS2. Oncogene, v. 32, n. 37, p. 4355–4365.

POWELL, J., MOTA, F., STEADMAN, D., SOUDY, C., MIYAUCHI, J. T., et al. (2018). Small molecule neuropilin-1 antagonists combine antiangiogenic and antitumor activity with immune modulation through reduction of transforming growth factor beta (TGF?) production in regulatory T-cells. J. Med. Chem., v. 61, n. 19, p. 4135-4154.

POZZI, A., YURCHENCO, P. D., and IOZZO, R. V. (2017). The nature and biology of basement membranes. Matrix Biol., p. 57–58, 1–11.

PROVENZANO, P. P., CUEVAS, C., CHANG, A. E., GOEL, V. K., VON HOFF, D. D., et al. (2012). Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell., v. 21, n. 3, p. 418–429.

PROVENZANO, P. P., INMAN, D. R., ELICEIRI, K. W., KNITTEL, J. G., YAN, L., et al. (2008). Collagen density promotes mammary tumor initiation and progression. BMC Med., v. 6, p. 11.

PUCCI-MINAFRA, I., and LUPARELLO, C. (1991). Type V/type I collagen interactions in vitro and growth-inhibitory effect of hybrid substrates on 8701-BC carcinoma cells. J. Submicrosc. Cytol. Pathol., v. 23, n.1, p. 67–74.

QIAN, L.W., MIZUMOTO, K., URASHIMA, T., NAGAI, E., MAEHARA, N., et al. (2002). Radiation-induced increase in invasive potential of human pancreatic cancer cells and its blockade by a matrix metalloproteinase inhibitor, CGS27023. Clin Cancer Res., v. 8, n. 4, p. 1223–7.

QUAIL, D.F., and JOYCE, J.A. (2013). Microenvironmental regulation of tumor progression and metastasis. Nat Med., v. 19, n. 11, p. 1423-37.

RAAVÉ, R., VAN KUPPEVELT, T. H., and DAAMEN, W. F. (2018). Chemotherapeutic drug delivery by tumoral extracellular matrix targeting. J. Control. Release, v. 274, p. 1-8.

RAHAL, O. M., WOLFE, A. R., MANDAL, P. K., LARSON, R., TIN, S., et al. (2018). Blocking interleukin (IL) 4-and IL13-mediated phosphorylation of STAT6 (Tyr641) decreases M2 polarization of macrophages and protects against macrophage-mediated radioresistance of inflammatory breast cancer. Int J Radiat Oncol Biol Phys., v. 100, n. 4, p. 1034-1043.

RAMMENSEE, H-G., and SINGH-JASUJA, H. (2013). HLA ligandome tumor antigen discovery for personalized vaccine approach. Expert Rev. Vaccines, v. 12, n. 10, p. 1211-7.

REINA-CAMPOS, M., MOSCAT, J., and DIAZ-MECO, M. (2017). Metabolism Shapes the Tumor Microenvironment. Curr Opin Cell Biol., v. 48, p. 47-53.

RICE, A. J., CORTES, E., LACHOWSKI, D., CHEUNG, B. C. H., KARIM, S. A., et al. (2017). Matrix stiffness induces epithelial-mesenchymal transition and promotes chemoresistance in pancreatic cancer cells. Oncogenesis, v. 6, n. 7, p. e352.

RÖHRIG, F., VORLOVÁ, S., HOFFMANN, H., WARTENBERG, M., ESCORCIA, F. E., et al. (2017). VEGF-ablation therapy reduces drug delivery and therapeutic response in ECM-dense tumors. Oncogene, v. 36, n. 1, p. 1–12.

ROSEN, O.M. (1987). After insulin binds. Science, v. 237, n. 4821, p. 1452-8.

ROSSOW, L., VEITL, S., VORLOVÁ, S., WAX, J. K., KUHN, A. E., et al. (2018). LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy. Oncogene, v. 37, n. 36, p. 4921–4940.

RUBIN, P., JOHNSTON, C.J., WILLIAMS, J.P., MCDONALD, S., and FINKELSTEIN, J.N. (1995). A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys., v. 33, n. 1, p. 99–109.

RUELLA, M., KLICHINSKY, M., KENDERIAN, S. S., SHESTOVA, O., ZIOBER, A., et al. (2017). Overcoming the immunosuppressive tumor microenvironment of hodgkin lymphoma using chimeric antigen receptor T cells. Cancer Discov., v. 7, n. 10, p. 1154-1167.

SALMON, H., and DONNADIEU, E. (2012). Within tumors, interactions between T cells and tumor cells are impeded by the extracellular matrix. Oncoimmunology, v. 1, n. 6, p. 992-994

SALMON, H., FRANCISZKIEWICZ, K., DAMOTTE, D., DIEU-NOSJEAN, M. C., VALIDIRE, P., et al. (2012). Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J. Clin. Invest., v. 122, n. 3, p. 899-910.

SCHAAF, M. B., GARG, A. D., and AGOSTINIS, P. (2018). Defining the role of the tumor vasculature in antitumor immunity and immunotherapy. Cell Death Dis., v. 9, n. 2, p. 115.

SCHELESSINGER, J. (1988). Signal transduction by allosteric receptor oligomerization. Trends Biochem Sci., v. 13, n. 11, p. 443-7.

SCHOBER, M., JESENOFSKY, R., FAISSNER, R., WEIDENAUER, C., HAGMANN, W., et al. (2014). Desmoplasia and chemoresistance in pancreatic cancer. Cancers (Basel.), v. 6, n. 4, p. 2137–2154.

SCHÜTZE, F., RÖHRIG, F., VORLOVÁ, S., GATZNER, S., KUHN, A., et al. (2015). Inhibition of lysyl oxidases improves drug diffusion and increases efficacy of cytotoxic treatment in 3D tumor models. Sci. Rep., v 5, p. 17576.

SCHWARTZ, M.A. (2010). Integrins and extracellular matrix in mechanotransduction. Cold Spring Harb. Perspect. Biol., v. 2, n. 12, p. a005066.

SIDDIKUZZAMAN, GRACE, V. M., and GURUVAYOORAPPAN, C. (2011). Lysyl oxidase: a potential target for cancer therapy. Inflammopharmacology, v. 19, n. 3, p. 117–129.

SINGH, A., and SETTLEMAN, J. (2010). EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene, v. 29, n. 34, p. 4741-51.

SHEN, C.J., SHARMA, A., VUONG, D-V., ERLER, J.T., PRUSCHY, M., et al. (2014). Ionizing radiation induces tumor cell lysyl oxidase secretion. BMC Cancer, v. 14, p. 532.

SMITH-MUNGO, L. I., and KAGAN, H. M. (1998). Lysyl oxidase: properties, regulation and multiple functions in biology. Matrix Biol., v. 16, n. 7, p. 387–398.

SPEAKE, W.J., DEAN, R.A., KUMAR, A., MORRIS, T.M., SCHOLEFIELD, J.H., et al. (2005). Radiation induced MMP expression from rectal cancer is short lived but contributes to in vitro invasion. Eur J Surg Oncol., v. 31, n. 8, p. 869–74.

SUN, D., WANG, X., ZHANG, H., DENG, L., and ZHANG, Y. (2011). MMP9 mediates MICA shedding in human osteosarcomas. Cell Biol. Int., v. 35, n. 6, p. 569-74.

TARIQ, M., ZHANG, J., LIANG, G., DING, L., HE, Q., et al. (2017). Macrophage polarization: anti-cancer strategies to target tumor-associated macrophage in breast cancer. J. Cell. Biochem., v. 118, n. 9, p. 2484-2501.

THIERY, J.P., ACLOQUE, H., HUANG, R.Y.J., and NIETO, M.A. (2009). Epithelial-mesenchymal transitions in development and disease. Cell, v. 139, n. 5, p. 871-90.

VANPOUILLE-BOX, C., DIAMOND, J.M., PILONES, K.A., ZAVADIL, J., BABB, J.S., et al. (2015). TGF? is a master regulator of radiation therapy-induced antitumor immunity. Cancer Res., v. 75, n. 11, p. 2232–42.

VORON, T., COLUSSI, O., MARCHETEAU, E., PERNOT, S., NIZARD, M., et al. (2015). VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J. Exp. Med., v. 212, n. 2, p. 139-48.

WANG, Z., LI, Y., KONG, D., BANERJEE, S., AHMAD, A., et al. (2009). Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Res., v. 69, n. 6, p. 2400-7.

WALDHAUER, I., GOEHLSDORF, D., GIESEKE, F., WEINSCHENK, T., WITTENBRINK, M., et al. (2008). Tumor-associated MICA is shed by ADAM proteases. Cancer Res., v. 68, n. 15, p. 6368-76.

WALTER, C., DAVIS, J. T., MATHUR, J., and PATHAK, A. (2018). Physical defects in basement membrane-mimicking collagen-IV matrices trigger cellular EMT and invasion. Integr. Biol., v. 10, n. 6, p. 342–355.

WEI, S. C., FATTET, L., TSAI, J. H., GUO, Y., PAI, V. H., et al. (2015). Matrix stiffness drives epithelial-mesenchymal transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway. Nat. Cell Biol., v. 17, n. 5, p. 678–688.

WEI, J., WU, A., KONG, L. Y., WANG, Y., FULLER, G., et al. (2011). Hypoxia potentiates glioma-mediated immunosuppression. PLoS One, v. 6, n. 1, p. e16195.

WELTER, M., and RIEGER, H. (2013). Interstitial fluid flow and drug delivery in vascularized tumors: a computational model. PLoS ONE, v. 8, n. 8, p. e70395.

WENNERBERG, E., LHUILLIER, C., VANPOUILLE-BOX, C., PILONES, K. A., GARCÍA-MARTÍNEZ, E., et al. (2017). Barriers to radiation-induced in situ tumor vaccination. Front Immunol., v. 8, p. 229.

WESLEY II, R. B., MENG, X., GODIN, D., and GALIS, Z. S. (1998). Extracellular matrix modulates macrophage functions characteristic to atheroma: collagen type I enhances acquisition of resident macrophage traits by human peripheral blood monocytes in vitro. Arterioscler. Thromb. Vasc. Biol., v. 18, n. 3, p. 432-40.

WU, H.J., HAO, M., YEO, S.K., and GUAN,J.L. (2020). FAK signaling in cancer-associated fibroblasts promotes breast cancer cell migration and metastasis by exosomal miRNAs-mediated intercellular communication. Oncogene, v. 39, n. 12, p. 2539-2549.

WU, Y.J., LIN, S.H., DIN, Z.H., SU, J.H., and LIU, C.I. (2019). Sinulariolide Inhibits Gastric Cancer Cell Migration and Invasion through Downregulation of the EMT Process and Suppression of FAK/PI3K/AKT/mTOR and MAPKs Signaling Pathways. Mar Drugs., v. 17, n. 12, p. 668.

XIE, J., JIANG, J., ZHANG, Y., XU, C., YIN, L., et al. (2012). Up-regulation expressions of lysyl oxidase family in anterior cruciate ligament and medial collateral ligament fibroblasts induced by transforming growth factor-beta 1. Int Orthop., v. 36, n.1, p. 207-13.

XU, J., ZHU, W., CHEN, L., and LIU, L. (2018). MicroRNA 433 inhibits cell growth and induces apoptosis in human cervical cancer through PI3K/AKT signaling by targeting FAK. Oncol Rep., v. 40, n. 6, p. 3469-3478.

YANG, J., MANI, S.A., DONAHER, J.L., RAMASWAMY, S., ITZYKSON, R.A., et al. (2004). Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell, v. 117, n. 7, p. 927-39.

YANG, W., and XIA, S-H. (2006). Mechanisms of regulation and function of G-protein-coupled receptor kinases. World J Gastroenterol., v. 12, n. 48, p. 7753–7757.

YURCHENCO, P. D. (2011). Basement membranes: cell scaffoldings and signaling platforms. Cold Spring Harb. Perspect. Biol., v. 3, n. 2, p. a004911.

ZAFFRYAR-EILOT, S., MARSHALL, D., VOLOSHIN, T., BAR-ZION, A., SPANGLER, R., et al. (2013). Lysyl oxidase-like-2 promotes tumour angiogenesis and is a potential therapeutic target in angiogenic tumours. Carcinogenesis, v. 34, n. 10, p. 2370–2379.

ZAGHDOUDI, S., DECAUP, E., BELHABIB, I., SAMAIN, R., CASSANT-SOURDY, S., et al. (2020). FAK activity in cancer?associated fibroblasts is a prognostic marker and a druggable key metastatic player in pancreatic cancer. EMBO Mol Med., v. 12, n. 11, p. e12010.

ZHANG, F., WANG, H., WANG, X., JIANG, G., LIU, H., et al. (2016). TGF-? induces M2-like macrophage polarization via SNAIL-mediated suppression of a pro-inflammatory phenotype. Oncotarget., v. 7, n. 32, p. 52294-52306.

ZHANG, H., REN, L., DING, Y., LI, F., CHEN, X., et al. (2019). Hyaluronan-mediated motility receptor confers resistance to chemotherapy via TGF?/Smad2-induced epithelial-mesenchymal transition in gastric cancer. FASEB J., v. 33, n. 5, p. 6365–6377.

ZNATI, C.A., ROSENSTEIN, M., MCKEE, T.D., BROWN, E., TURNER, D., et al. (2003). Irradiation reduces interstitial fluid transport and increases the collagen content in tumors. Clin Cancer Res., v. 9, n. 15, p. 5508-13.

ZODE, G. S., CLARK, A. F., and WORDINGER, R. J. (2009). Bone morphogenetic protein 4 inhibits TGF-?2 stimulation of extracellular matrix proteins in optic nerve head cells: role of gremlin in ECM modulation. Glia, v. 57, n. 7, p. 755–766.

Published

08/17/2021

How to Cite

BARBOSA, A. E. da S.; -MARTINS, J. M. A.; LOPES, B. A.; GIARDINI, I. J. M.; -HALDER, C. V. F. Plasticidade molecular da matriz extracelular contribui para metástase e resistência a terapias / Molecular plasticity of the extracellular matrix contributes to metastasis and resistance to therapies. Brazilian Journal of Health Review, [S. l.], v. 4, n. 4, p. 17640–17670, 2021. DOI: 10.34119/bjhrv4n4-250. Disponível em: https://ojs.brazilianjournals.com.br/ojs/index.php/BJHR/article/view/34650. Acesso em: 20 oct. 2026.

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Original Papers