Alternagin-C, an alpha2beta1 integrin ligand, attenuates collagen-based adhesion, stimulating the metastasis suppressor 1 expression in triple-negative breast tumor cells

Autor(es)

Moritz, Milene Nobrega de Oliveira ; Casali, Bruna Carla ; Stotzer, Uliana Sbeguen ; dos Santos, Patty Karina ; Selistre-de-Araujo, Heloisa Sobreiro

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 210, p. 10-pg., 2022-04-30.

Resumo

Triple-negative breast cancer has an aggressive clinical course and its treatment has been challenging due to high metastatic risk. Molecular targets have been sought to provide better strategies for this type of cancer. Integrins are cell adhesion receptors involved in tumor progression and alpha(2)beta(1) integrin, a collagen receptor, has a key role in breast metastasis. Disintegrins, a family of proteins from snake venoms, selectively block the function of integrin receptors. Alternagin-C (ALT-C), a disintegrin-like protein purified from Bothrops alternatus venom, binds to alpha(2)beta(1) integrin, attenuating inflammation and angiogenesis, and decreasing metalloprotease levels in the tumor microenvironment, which suggests anti-metastatic effects. However, its mechanisms of action in metastatic tumor cells have not been fully explored. Here, we investigated ALT-C effects in a triple-negative breast cancer cell line (MDA-MB-231) to elucidate how alpha 2 beta 1 integrin affects cellular adhesion, migration and gene expression related to metastasis. We observed that ALT-C attenuated cell adhesion of MDA-MB-231 cells to collagen I. alpha 2 integrin subunit silencing in MDA-MB-231 cells did not inhibit cell adhesion and migration to collagen I, indicating that other integrins play a crucial role in cell motility for this cell line. ALT-C also stimulated the metastasis suppressor 1 (MTSS1) expression and decreased metalloproteases MMP9 and MMP2. Therefore, we suggest that ALT-C contributes to impair metastasis, preventing extracellular matrix degradation and tumor attachment to collagen I, increasing MTSS1. This study is the first to elucidate the anti-metastatic mechanism involving a disintegrin-like protein from snake venom targeting alpha 2 beta 1 integrin and stimulating a metastasis suppressor. (AU)

• Processo FAPESP: 13/00798-2 - A matriz extracelular no envelhecimento, no exercício e no microambiente tumoral
• Beneficiário: Heloisa Sobreiro Selistre de Araújo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/17651-7 - A integrina alfa2beta1 na progressão tumoral mamária: papel no microambiente tumoral e na metástase
• Beneficiário: Milene Nóbrega de Oliveira Moritz
• Modalidade de apoio: Bolsas no Brasil - Doutorado