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Integrin molecular mechanisms of action during tumor progression and metastasis development: an intercellular approach

Abstract

Integrins are heterodimeric cell surface receptors that connect cells to the extracellular matrix (ECM) and control various processes such as cell migration, cytoskeletal organization, cell polarity, metalloprotease activity, collagen synthesis, and migration direction. The pattern of integrin expression may be greatly altered in cells that underwent tumor transformation when compared to normal cells. Integrin-mediated signaling also modulates the response triggered by the activation of growth factor receptors such as VEGF/VEGFR, resulting in pro- or anti-angiogenic signals depending on the pathway involved. Therefore, integrins have been studied as possible targets of pharmacological inhibition for the treatment of cancer and for the prevention of metastases. However, despite excellent results in preclinical trials, integrin inhibitors have not been successful in clinical trials, probably because of our limited knowledge of the molecular mechanisms of action of these receptors. In this project, we intend to contribute to the increase of knowledge of the role of avb3 and a2b1 integrins in the metastatic cascade. We will use in vitro models of co-culture to mimic the extravasation of tumor cells from the circulation and two well characterized disintegrins as specific ligands of these receptors. In addition, we will use a quasi-vivo system which will add complexity to the assay, similar to most in vivo assays. Functional, morphological and biochemical analysis will be performed, aiming also a search for new pharmaceutical targets for metastasis prevention or treatment. (AU)

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Scientific publications (9)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ALTEI, WANESSA FERNANDA; PACHANE, BIANCA CRUZ; SOUZA, CRISTIANO; MARQUES, MARCIA MARIA CHIQUITELLI; SELISTRE-DE-ARAUJO, HELOISA. New insights into the discovery of drugs for triple-negative breast cancer metastasis. EXPERT OPINION ON DRUG DISCOVERY, v. 17, n. 4, p. 12-pg., . (14/18747-8, 13/00798-2, 21/01983-4, 19/11437-7)
MORITZ, MILENE N. O.; MERKEL, ALYSSA R.; FELDMAN, EAN G.; SELISTRE-DE-ARAUJO, HELOISA S.; RHOADES (STERLING), JULIE A.. Biphasic alpha 2 beta 1 Integrin Expression in Breast Cancer Metastasis to Bone. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 13, . (13/00798-2, 19/11437-7, 17/23094-1)
ALTEI, WANESSA F.; PACHANE, BIANCA C.; MARTINS, LUCIMARA J.; GOMES, RALPH C.; SANTOS, RICARDO N.; FERNANDES, DANIARA C.; SELISTRE-DE-ARAUJO, HELOISA S.; COELHO, FERNANDO; ANDRICOPULO, ADRIANO D.. Synthetic Spirocyclohexadienones as New Anti-Migratory Compounds in Triple-Negative Breast Cancer Cell Migration. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 21, n. 14, p. 1901-1910, . (13/07600-3, 19/11437-7, 10/06741-4)
BACKES, EDUARDO HENRIQUE; PIRES, LAIS DE NOBILE; SELISTRE-DE-ARAUJO, HELOISA SOBREIRO; COSTA, LIDIANE CRISTINA; PASSADOR, FABIO ROBERTO; PESSAN, LUIZ ANTONIO. Development and characterization of printablePLA/beta-TCPbioactive composites for bone tissue applications. Journal of Applied Polymer Science, v. 138, n. 5, . (16/19978-9, 19/11437-7, 17/11366-7, 17/09609-9, 11/21313-1)
PACHANE, BIANCA CRUZ; CAETANO NUNES, ANA CAROLINA; CATALDI, THAIS REGIANI; MICOCCI, KELLI CRISTINA; MOREIRA, BIANCA CARUSO; LABATE, CARLOS ALBERTO; SELISTRE-DE-ARAUJO, HELOISA SOBREIRO; ALTEI, WANESSA FERNANDA. Small Extracellular Vesicles from Hypoxic Triple-Negative Breast Cancer Cells Induce Oxygen-Dependent Cell Invasion. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 20, p. 21-pg., . (21/01983-4, 17/06198-8, 19/11437-7, 19/05149-9, 19/17737-2)
DERIGGI-PISANI, GRAZIELE F.; STOTZER, ULIANA S.; MARQUETI, RITA C.; RODRIGUES, MARIA F. C.; BIFFE, BRUNA G.; SILVA, KARINA A.; FABRICIO, VICTOR; ROSEN, CLIFFORD J.; SELISTRE-DE-ARAUJO, HELOISA SOBREIRO. Role of resistance training in bone macro and micro damages in an estrogen absence animal model. Life Sciences, v. 317, p. 12-pg., . (19/11437-7)
CASALI, BRUNA C.; GOZZER, LARISSA T.; BAPTISTA, MATHEUS P.; ALTEI, WANESSA F.; SELISTRE-DE-ARAUJO, HELOISA S.. The Effects of alpha v beta 3 Integrin Blockage in Breast Tumor and Endothelial Cells under Hypoxia In Vitro. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 3, p. 16-pg., . (19/11437-7, 13/00798-2)
SELISTRE-DE-ARAUJO, HELOISA SOBREIRO; PACHANE, BIANCA CRUZ; ALTEI, WANESSA FERNANDA. | Tumor heterogeneity and the dilemma of antioxidant therapies in cancer. ANNALS OF TRANSLATIONAL MEDICINE, v. N/A, p. 5-pg., . (21/01983-4, 19/05149-9, 19/11437-7)
DA SILVA, ADILSON JOSE; CUNHA, JOSIVAN DE SOUZA; HREHA, TERI; MICOCCI, KELLI CRISTINA; SELISTRE-DE-ARAUJO, HELOISA SOBREIRO; BARQUERA, BLANCA; KOFFAS, MATTHEOS A. G.. Metabolic engineering of E. coli for pyocyanin production. METABOLIC ENGINEERING, v. 64, p. 15-25, . (19/11437-7, 17/09695-2)

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