El rol de VEGF en la Angiogénesis fisiológica y tumoral

Jhan Sebastián Saavedra Torres, Luisa Fernanda Zúñiga Cerón, Sofía Isabel Freyre Bernal, Guillermo Wilson Muñoz Ordoñez, Carolina Salguero

Resumen


El proceso de angiogénesis, en el cual se desarrollan nuevos vasos sanguíneos a partir de una red vascular existente, requiere de la activación de los receptores en la superficie de las células endoteliales. En sus procesos fisiológicos, como la reparación de heridas, se observa un aumento en la permeabilidad vascular que induce el depósito de proteínas plasmáticas en la matriz extracelular y favorece la reparación y la cicatrización. No obstante, en algunas patologías como el cáncer, desempeña un papel importante para el crecimiento y la diseminación de las células tumorales. Su activación en el tumor permite, pero no garantiza, la expansión tumoral y, por ende, la ausencia de angiogénesis puede limitar el crecimiento. Por eso, se han desarrollado varios inhibidores con el propósito de interferir específicamente en diferentes etapas de este proceso, por ejemplo, el bevacizumab (Avastin) que se distingue como un anticuerpo monoclonal que reconoce y se une al Factor de Crecimiento Endotelial Vascular (por sus siglas en inglés VEGF).

 

The role of VEGF in Physiological and tumoral angiogénesis

Abstract

Angiogenesis, the cellular process leading to the development of new blood vessels from an existing vascular network, requires activation of surface receptors of normal endothelial cells by signaling molecules such as the Vascular Endothelial Growth Factor (VEGF). During physiological processes of angiogenesis leading to injury repair, an increase of vascular permeability favors deposits of plasma proteins in the extracellular matrix. However, in pathological processes such as cancer, angiogenesis plays an important role in the growth and proliferation of the tumor cells. The activation of angiogenesis in a tumor induces, but does not guarantee, tumor expansion; hence, the absence of angiogenesis may limit the tumor growth. Angiogenesis inhibitors been developed to interfere with different stages of the process. For example, bevacizumab (Avastin) is recognized as a monoclonal antibody binds specifically to VEGF and inhibits its angiogenic function.


Palabras clave


Factor de crecimiento endotelial vascular (VEGF), angiogénesis fisiológica, angiogénesis patológica, cáncer, metástasis, metaloproteinasas de la matriz (MMP), proliferación celular, Vascular Endothelial Growth Factor (VEGF), physiologic angiogenesis

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Referencias


René. L. Angiogenesis and cancer. Medwave. 2007; 3 (1): 3546.

Peter C. Angiogenesis in life, disease and medicine. Nature. 2005; 438 (1): 932- 6.3.

Jiménez-Andrade G y Espinosa C. Inflamación y angiogénesis : el papel facilitador de las células cebadas en el desarrollo del melanoma. Medigraphic. 2011;6 (235): 111- 9.4.

Sánchez-Socarrás V. Papel de la angiogénesis en el crecimiento tumoral. Rev Cuba Invest Biomed. 2001; 20 (3): 310.5.

Hayden EC. “Cutting off cancer’s supply lines”. Nature. (s.f.); 458 (7239): 686-7. doi:10.1038/458686b. PMID 19360048.

Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro- Angiogenic Therapies. Genes Cancer. 2011; 2 (12): 1097- 105.7.

Lacoste J, Aprikian AG, Chevalier S. Focal adhesion kinase is required for bombesin-induced prostate cancer cell motility. Mol Cell Endocrinol. 2005 May; 235 (1- 2): 51- 61. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/15866427

American Cancer Society. Cancer Facts and Figures. 1 ed. Atlanta: American Cancer Society: 2015; 3- 7.

DeVita VT Jr., Lawrence TS., Rosenberg. SA. Cancer: principles & practice of oncology. 8va ed. Philadelphia: Wolters Kluwer: 2008.10.

Gupta GP. Cancer metastasis: building a framework. Cell. 2006; 127 (1): 679- 95.11.

Duffy AM. Vascular Endothelial Growth Factor (VEGF) and Its Role in Non-Endothelial Cells: Autocrine Signalling by VEGF. Firts. Madame Curie Bioscience Database. USA: Bioscience.

Reichardt LF. Extracellular matrix molecules and their receptors: Functions in neural development. Annu Rev Neurosci. 1991; 14 (1): 531- 70.13.

Edward M. Conway. Molecular mechanisms of blood vessel growth. Cardiovasc Res. 2001; 49 (1): 507- 21.14.

Kumar V, Abbas A, Fausto N, Aster JC. Patología Estructural y Funcional Robbins y Cotran. 8va Ed. Barcelona, España: Elsevier Saunders; 2010. 117; 120- 669 pp.

Jiménez Cuenca B. Mecanismo de inhibición de la angiogénesis tumoral por trombospondina-1. Nefrología. 2003; 23 (Supl. 3): 49- 53.16.

Yancopoulos GD., Davis S., Gale NW., Rudge JS., Wiegand SJ. HJ. Vascular-specific growth factors and blood vessel formation. Nature. 2000; 407 (1): 242- 8.

Dvorak HF. Angiogenesis: update 2005. J Thromb Haemost. 2005; 3 (1):1835- 42.18.

Martínez-Hezquerro JD, Herrera LA. Angiogénesis: VEGF/VEGFRs como blancos terapéuticos en el tratamiento contra el cáncer. Cancerología. 2006; 1 (1): 83- 96.19.

Thakker GD. HD. The role of phosphatidylinositol 3-kinase in vascular endotelial growth factor signaling. J Biol Chem. 1999; 274 (1): 10002- 7.20.

Ferrara N, Gerber PH. The biology of VEGF and its receptors. Nat Med. 2003; 9 (6): 669- 76. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/12778165

Folkman J. DJV. Cáncer: Principios y Práctica de Oncología. Vol 2. 7a Ed. Philadelphia: PA: Lippincott Williams & Wilkins; 2005. 2865- 2882 pp.23.

Napoleone Ferrara. Vascular Endothelial Growth Factor: Basic Science and Clinical Progress. Endocr Rev. 2003; 25 (4).

Dejana E, Orsenijo F, Lampugnani MG. The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci. 2008; 121 (Pt 13):2115- 22.25.

Weis SM. CD. Pathophysiological consequences of VEGF-induced vascular permeability. Nature. 2005; 437 (7058): 497- 504.26.

Nelson WJ. Regulation of cell-cell adhesion by the cadherin-catenin complex. Biochem Soc Trans. 2008; 36 (Pt 2): 149- 55.27.

Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005; 307 (5706): 58- 62.28.

Alon T. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med. 1995; 1 (1): 1024- 8.29.

Safran M. KJW. HIF hydroxylation and the mammalian oxygen-sensing pathway. J Clin Invest. 2003; 111 (1): 779- 83.30.

Berra E., Ginouves A. PJ. The hipoxia-inductible-factor hydroxylases bring fresh air into hipoxia signalling. EMBO Rep. 2006; 7 (1): 41- 5.31.

Liu. Y. Hypoxia Regulates Vascular Endothelial Growth Factor Gene Expression in Endothelial Cells. Circ Res. 1995; 77 (1): 638- 43.32.

Shing Y, Folkman J, Sullivan R, Butterfield C. Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science. 1984; 223 (1): 1296- 9.33.

Folkman J y Klagsbrun M. Angiogenic factors. Science. 1987; 235 (1): 442- 7.

Inoue M. VEGF-A has a critical, nonredundant role in angiogenic switching and pancreatic beta cell carcinogenesis. Cancer Cell. 1(2):193- 202.

Rini BI. Biology and clinical development of vascular endothelial growth factor-targeted therapy in renal cell carcinoma. J Clin Oncol. 2005; 23 (5): 1028- 43.36.

Giraudo E., Primo L., Audero E., Gerber HP. Tumor necrosis factor alfa regula la expresión de receptor vascular-2 del factor de crecimiento endotelial y de su cooperación receptor neuropilina-1 en las células endoteliales vasculares humanas. J Biol Chem. 1998; 273 (1): 22128- 35.37.

Hoeben A, Landuyt B. Vascular Endotelial Growth Factor y la angiogénesis. Pharmacol Rev. 2004; 56 (4): 549- 80.38.

(agregar autores). Papel del VEGF en la respuesta celular a la agresión. Nefrología. 2003; 23 (Supl 3): 54- 7.39.

Gerber HP, McMurtrey AK. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3’-kinase/Akt signal transduction pathway. Requirement for Flk1/KDR activation. J Biol Chem. 1998; 273 (46): 30336- 43.

Brazil DP, Park J. HB. PKB binding proteins. Getting in on the Akt. Cell. 2002; 111: (1): 293- 303.41.

Mezquita C. Biología Molecular del Cáncer. Conoc web net. 2001. (Completar referencia)

Harris AL. Hypoxia-a key regulatory factor in tumor growth. Nat Rev Cancer. 2002; 2 (1): 38- 47.43.

Jones N (completar referencia). Tie receptors: new modulators of angiogenic and lymphangiogenic responses. Nat Rev. 2001; 257 (2).(agregar paginage)

Hu B, Cheng SY. Angiopoyetina-2: Desarrollo de inhibidores para la terapia del cáncer. Curr Oncol Rep. 2009; 11 (2): 111- 6.45.

Mezquita J, Mezquita B PM and MC. Characterization of a novel form of angiopoietin-2 (Ang-2B) and expression of VEGF and angiopoietin-2 during chicken testicular development and regression. PubMed. 1999; 260: 492- 8.

Mezquita J, Mezquita, P, Pau M, Mezquita B, Francone V, Vilagrasa X. Genomic structure and alternative splicing of chicken Angiopoietin-2. PubMed. 2000; 275: 643-51.47.

Cheresh D a, Stupack DG. Regulation of angiogenesis: apoptotic cues from the ECM. Oncogene. 2008; 27 (48): 6285- 98. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/18931694

Weis S, Cui J, Barnes L. Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol. 2004;167 (1): 223- 9.

Eliceiri BP., Klemke R., Stromblad S. CD. Integrin alpha- vbeta3 requirement for sustained mitogen-activated protein kinase activity during angiogenesis. J Cell Biol. 140 (1): 1255- 63.50.

Benavides J. Reparación de heridas cutáneas. Rev Asoc Col Dermatol. 2006; 16 (1): 29- 35.51.

Teller P. Fisiología de la cicatrización de la herida: de la lesión a la maduración. Surg Clin N Am, Elsevier España. 89 (1): 599- 610.52.

Michael J. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. TRENDS Pharmacol Sci. 22 (4): 201- 7.

Anna-Karin Olsson. AD. VEGF receptor signalling in control of vascular function. Nat Rev Mol Cell Biol. 7 (1): 359- 71.

Gialeli C, Theocharis AD. KN. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS. 2011; 278: 16- 27.

Van Damme J, Struyf S. Chemokineprotease interaccions in cancer. Semin Cancer Biol. 2004; 14: 201- 8.56.

Bourboulia D. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion. Semin Cancer Biol. 2010; 20: 161- 8.57.

Noël A, Jost M. Matrix metalloproteinases at cancer tumor-host interface. Semin Cell Dev Biol. 2008; 19: 52- 60.58.

Chabottaux V. Breast cancer progression: insights into multifaceted matrix metalloproteinases. Clin Exp Metastasis. 2007; 24: 647- 56.59.

Decock J., Hendrickx W., Vanleeuw U. et al. Plasma MMP1 and MMP8 expression in breast cancer: protective role of MMP8 against lymph node metastasis. BMC Cancer. 2008; 8: 77.60.

Egeblad M. WZ. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002; 2: 161- 74.61.

Gonzalez LO, Corte MD, Vásquez J.(completar tres autores más y luego si reportar el et al) Study of matrix metalloproteinases and their tissue inhibitors in ductal in situ carcinomas of the breast. Histopathology. 2008; 53: 403- 15.62.

Hua H, Li M, Luo T, Yin Y. Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci. 2011; 68: 3853- 68.63.

Sounni NE, Paye A, Host L. MT-MMPS as regulators of vessel stability associated with angiogenesis. Front Pharmacol. 2011; 2: 111.64.

Patterson BC. Angiostatin-converting enzyme activities of human matrilysin (MMP-7) and gelatinase B/ Type IV collagenase (MMP-9). J Biol Chem. 1997; 272: 23- 5.65.

Lin HC, Chang JH, Jain S, (completar tres autores más y luego si reportar el et al) et al. Matrilysin cleavage of corneal collagen type XVIII NC1 domain and generation of a 28-kDa fragment. Invest Ophthalmol Vis Sci. 2001; 42: 2517- 24.66.

Coronato S, Laguens G. Rol de las metaloproteinasas y sus inhibidores en patología tumoral. Med (Buenos Aires). 2012; 72: 495- 502.67.

Villanueva MT. Angiogenesis: Going with the flow. Nat Rev Cancer. Nature Research. 2016 Nov; 16 (12): 751- 751. Disponible en: http://www.nature.com/doifinder/10.1038/nrc.2016.127

American Cancer Society. Anti-angiogenesis Treatment. American Cancer Society. 2009. p. 3- 10.

Montes-Vera MR. Aspectos farmacocinéticos de bevacizumab. Rev Hosp Jua Mex. 2013; 80 (1): 73- 8.70.

Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011; 473 (7347): 298- 307. Disponible en: http://dx.doi.org/10.1038/nature10144

Khosravi Shahi P, del Castillo Rueda A. Angiogénesis neoplásica Neoplastic angiogenesis. An Med Interna. 2008; 25 (7).

EMA /An agency of the European Union. AVASTIN® (bevacizumab). European Medicines Agency. Firts. United Kingdom; 2015. p. 1- 5.

Meza-Junco J, Montaño-Loza A, Aguayo-González Á. Bases moleculares del cáncer. 2006; 58 (1): 56- 70.74.

Komarova NL, Wodarz D. Cancer as a microevolutionary process. Evol Heal Dis. 2010; (May 2014):1- 17.

Acharya Suchitra S. Exploration of the pathogenesis of haemophilic joint arthropathy: Understanding implications for optimal clinical management. Br J Haematol. 2012; 156 (1): 13- 23.76.

Camacho Damata X, Cabral P. Angiogénesis Tumoral : estrategias diagnósticas y terapéuticas. Salud Mil. 2012; 31 (1): 1-16.

Lee JJ, Lotze MT. Molecular basis of metastasis. N Engl J Med. 2009; 360 (16): 1679.

Brooks S a, Lomax-Browne HJ, Carter TM, Kinch CE, Hall DMS. Molecular interactions in cancer cell metastasis. Acta Histochem. Elsevier; 2010 Ene; 112 (1): 3- 25. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/19162308

Qian Q, Zhan P, Yu L, Shi Y, Cheng J, Wei S, et al. Baseline levels and decrease in serum soluble intercellular adhesion molecule-1 during chemotherapy predict objective response and survival in patients who have advanced non-small-cell lung cancer. Clin Lung Cancer. 2011 Mar; 12 (2): 131- 7.Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/21550560

Fontana VJ. Cancer immunology. Cutis. 1974; 13 (5): 717- 8.




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