| Full text | |
| Author(s): Show less - |
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
Total Authors: 11
|
| Document type: | Journal article |
| Source: | NEOPLASIA; v. 30, p. 13-pg., 2022-08-01. |
| Abstract | |
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) | |
| FAPESP's process: | 14/10492-0 - Hippo-YAP as a converging pathway for biochemical and mechanical signals from the extracellular matrix during mammary gland morphogenesis and breast cancer progression |
| Grantee: | Alexandre Bruni Cardoso |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 17/25437-3 - High-throughput identification of genes that mediate cell quiescence induced by laminin |
| Grantee: | Mayara Carolinne Silva Botelho |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 14/25832-1 - Hippo-YAP pathway as a mediator of extracellular matrix signals in non-malignant and malignant epithelial cells of the mammary gland |
| Grantee: | Ana Paula Zen Petisco Fiore |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 19/26767-2 - Proteostasis regulation of MST2 in the Hippo pathway |
| Grantee: | Alexandre Bruni Cardoso |
| Support Opportunities: | Regular Research Grants |