Prognostic value of integrin alpha V expression and localization pattern in invasive breast carcinomas

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Cerqueira, Otto Luiz Dutra ; Botelho, Mayara Carolline Silva ; Fiore, Ana Paula Zen Petisco ; Osorio, Cynthia Aparecida Bueno de Toledo ; Tomasin, Rebeka ; Morais, Mauro Cesar Cafundo ; Lopez, Rossana Veronica Mendoza ; Cardoso, Elaine Cristina ; Vilella-Arias, Santiago Andres ; Reis, Eduardo Moraes ; Bruni-Cardoso, Alexandre

• Tipo de documento: Artigo Científico
• Fonte: NEOPLASIA; v. 30, p. 13-pg., 2022-08-01.

Resumo

Invasion of surrounding stroma is an early event in breast cancer metastatic progression, and involves loss of cell polarity, loss of myoepithelial layer, epithelial-mesenchymal transition (EMT) and remodeling of the extracellular matrix (ECM). Integrins are transmembrane receptors responsible for cell-ECM binding, which triggers signals that regulate many aspects of cell behavior and fate. Changes in the expression, localization and pairing of integrins contribute for abnormal responses found in transformed epithelia. We analyzed 345 human breast cancer samples in tissue microarrays (TMA) from cases diagnosed with invasive breast carcinoma to assess the expression and localization pattern of integrin alpha V and correlation with clinical parameters. Patients with lower levels of integrin alpha V staining showed reduced cancer specific survival. A subset of cases presented a peripheral staining of integrin alpha V surrounding tumor cell clusters, possibly matching the remaining myoepithelial layer. Indeed, the majority of ductal carcinoma in situ (DCIS) components found in the TMA presented integrin alpha V at their periphery, whereas this pattern was mostly lost in invasive components, even in the same sample. The lack of peripheral integrin alpha V correlated with decreased cancer specific survival. In addition, we observed that the presence of integrin alpha V in the stroma was an indicative of poor survival and metastatic disease. Consistently, by interrogating publicly available datasets we found that, although patients with higher mRNA levels of integrin alpha V had increased risk of developing metastasis, high co-expression of integrin alpha V and a myoepithelial cell marker (MYH11) mRNA levels correlated with better clinical outcomes. Finally, a 3D cell culture model of non-malignant and malignant cells reproduced the integrin alpha V pattern seen in patient samples. Taken together, our data indicate that both the expression levels of integrin alpha V and its tissue localization in primary tumors have prognostic value, and thus, could be used to help predict patients at higher risk of developing metastasis.& nbsp; (AU)

• Processo FAPESP: 14/10492-0 - Hippo-YAP como uma via de convergência dos sinais bioquímicos e mecânicos provenientes da matriz extracelular durante a morfogênese da glândula mamária e a progressão do câncer de mama
• Beneficiário: Alexandre Bruni Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 17/25437-3 - Identificação em larga escala de genes que medeiam a quiescência celular induzida pela laminina
• Beneficiário: Mayara Carolinne Silva Botelho
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/25832-1 - A via Hippo-YAP como mediadora de sinais bioquímicos da matriz extracelular em células epiteliais não-malignas e malignas da glândula mamária
• Beneficiário: Ana Paula Zen Petisco Fiore
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/26767-2 - Regulação da proteostase de MST2 na via Hippo
• Beneficiário: Alexandre Bruni Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular