Blocking αvβ3 integrin by a recombinant RGD disintegrin impairs VEGF signaling in endothelial cells

Biochimie
Cyntia F MontenegroH S Selistre-de-Araujo

Abstract

Vascular endothelial growth factor (VEGF) and αvβ3 integrin are key molecules that actively participate in tumor angiogenesis and metastasis. Some integrin-blocking molecules are currently under clinical trials for cancer and metastasis treatment. However, the mechanism of action of such inhibitors is not completely understood. We have previously demonstrated the anti-angiogenic and anti-metastatic properties of DisBa-01, a recombinant His-tag RGD-disintegrin from Bothrops alternatus snake venom in some experimental models. DisBa-01 blocks αvβ3 integrin binding to vitronectin and inhibits integrin-mediated downstream signaling cascades and cell migration. Here we add some new information on the mechanism of action of DisBa-01 in the tumor microenvironment. DisBa-01 supports the adhesion of fibroblasts and MDA-MB-231 breast cancer cells but it inhibits the adhesion of these cells to type I collagen under flow in high shear conditions, as a simulation of the blood stream. DisBa-01 does not affect the release of VEGF by fibroblasts or breast cancer cells but it strongly decreases the expression of VEGF mRNA and of its receptors, vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2) in endothelial cells. DisBa-01...Continue Reading

References

Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·B Felding-HabermannB M Mueller
Apr 11, 2002·Nature Cell Biology·Cindy K Miranti, Joan S Brugge
Jul 26, 2003·Cell Communication & Adhesion·Stephanie SchmitmeierThomas C Chen
Mar 17, 2004·Seminars in Cancer Biology·Arthur M MercurioJun Chung
Mar 22, 2005·Toxicon : Official Journal of the International Society on Toxinology·Rong-Sen YangWen-Mei Fu
Dec 13, 2005·Experimental Cell Research·Masabumi Shibuya, Lena Claesson-Welsh
Apr 25, 2006·Nature Reviews. Molecular Cell Biology·Anna-Karin OlssonLena Claesson-Welsh
Aug 8, 2006·Nature Medicine·Patricia S Steeg
Aug 23, 2006·Journal of Mammary Gland Biology and Neoplasia·Arthur M MercurioRobin E Bachelder
Sep 28, 2006·Journal of Biochemistry and Molecular Biology·Masabumi Shibuya
Sep 14, 2007·Nature Reviews. Cancer·Carlos López-Otín, Lynn M Matrisian
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Alexandre KauskotArnaud Bonnefoy
Jul 4, 2008·Nature Reviews. Cancer·Lee M Ellis, Daniel J Hicklin
Aug 21, 2008·International Journal of Cancer. Journal International Du Cancer·Meghan C BrownCezary Marcinkiewicz
Oct 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lee M Ellis, Daniel J Hicklin
Dec 31, 2008·Journal of Experimental & Clinical Cancer Research : CR·Leticia Oliveira-FerrerGunter Schuch
Mar 24, 2009·Nature Medicine·Andrew R ReynoldsKairbaan M Hodivala-Dilke
May 5, 2009·Cancer Cell·Sara M WeisDavid A Cheresh
Jul 29, 2009·Nature Reviews. Clinical Oncology·Axel Grothey, Evanthia Galanis
Aug 13, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John M L EbosRobert S Kerbel
Dec 24, 2009·Nature Reviews. Cancer·Jay S Desgrosellier, David A Cheresh
Jan 22, 2010·American Journal of Physiology. Cell Physiology·Sang Hun LeeHo Jae Han
Jan 28, 2010·Cancer Research·Laura M Vecchiarelli-FedericoYaacov Ben-David
Apr 24, 2010·Molecular Cancer·Maria Simona AguzziAntonio Facchiano
Aug 3, 2010·Toxicon : Official Journal of the International Society on Toxinology·Paula JuárezJohannes A Eble
Sep 21, 2010·Bone·Jochen G SchneiderKatherine N Weilbaecher
Dec 15, 2010·EMBO Molecular Medicine·Bernardo TavoraKairbaan M Hodivala-Dilke
Nov 10, 2011·Toxins·Heloisa S Selistre-de-AraujoAna Carolina B M Martin

❮ Previous
Next ❯

Citations

Jul 3, 2013·The International Journal of Biochemistry & Cell Biology·Cezary Marcinkiewicz
Jul 11, 2014·Anti-cancer Drugs·Cui-Cui SunZu-Hua Gao
Jan 1, 2013·Cell Adhesion & Migration·Lívia C A RibeiroIracilda Z Carlos
Dec 3, 2014·Toxicon : Official Journal of the International Society on Toxinology·Puebla Cassini-VieiraFernanda de Assis Araújo
Jan 18, 2017·International Journal of Biological Macromolecules·Denise de Oliveira GuimarãesVeridiana de Melo Rodrigues
Dec 4, 2019·Journal of Biomedical Materials Research. Part a·Martin HellerWalburgis Brenner
Apr 27, 2019·Frontiers in Surgery·Hakan Kulacoglu, Ferdinand Köckerling
Sep 30, 2020·Cell Communication and Signaling : CCS·Wanessa F AlteiHeloisa S Selistre-de-Araújo
Mar 22, 2019·Cell Communication and Signaling : CCS·Taís M DanilucciHeloisa S Selistre-de-Araujo
Aug 9, 2018·Toxins·Victor DavidRussolina Benedeta Zingali

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Biophysics of Adhesion

Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. It is also essential for infectious organisms, such as bacteria or viruses, to cause diseases. Understanding the biophysics of cell adhesion can help understand these diseases. Discover the latest research on the biophysics of adhesion here.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.