Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas
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 c...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558622000306 |
| _version_ | 1828832198228180992 |
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| author | Otto Luiz Dutra Cerqueira Mayara Carolline Silva Botelho Ana Paula Zen Petisco Fiore Cynthia Aparecida Bueno de Toledo Osório Rebeka Tomasin Mauro César Cafundó Morais Rossana Verónica Mendoza López Elaine Cristina Cardoso Santiago Andres Vilella-Arias Eduardo Moraes Reis Alexandre Bruni-Cardoso |
| author_facet | Otto Luiz Dutra Cerqueira Mayara Carolline Silva Botelho Ana Paula Zen Petisco Fiore Cynthia Aparecida Bueno de Toledo Osório Rebeka Tomasin Mauro César Cafundó Morais Rossana Verónica Mendoza López Elaine Cristina Cardoso Santiago Andres Vilella-Arias Eduardo Moraes Reis Alexandre Bruni-Cardoso |
| author_sort | Otto Luiz Dutra Cerqueira |
| collection | DOAJ |
| description | 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 αV and correlation with clinical parameters. Patients with lower levels of integrin αV staining showed reduced cancer specific survival. A subset of cases presented a peripheral staining of integrin αV 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 αV at their periphery, whereas this pattern was mostly lost in invasive components, even in the same sample. The lack of peripheral integrin αV correlated with decreased cancer specific survival. In addition, we observed that the presence of integrin αV 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 αV had increased risk of developing metastasis, high co-expression of integrin αV 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 αV pattern seen in patient samples. Taken together, our data indicate that both the expression levels of integrin αV 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. |
| first_indexed | 2024-12-12T16:49:12Z |
| format | Article |
| id | doaj.art-9bcfb0687f1f46b6a63f32c737d0a562 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-12-12T16:49:12Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-9bcfb0687f1f46b6a63f32c737d0a5622022-12-22T00:18:25ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862022-08-0130100803Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomasOtto Luiz Dutra Cerqueira0Mayara Carolline Silva Botelho1Ana Paula Zen Petisco Fiore2Cynthia Aparecida Bueno de Toledo Osório3Rebeka Tomasin4Mauro César Cafundó Morais5Rossana Verónica Mendoza López6Elaine Cristina Cardoso7Santiago Andres Vilella-Arias8Eduardo Moraes Reis9Alexandre Bruni-Cardoso10Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, 05508-900, Brasil; Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo (ICESP), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, 01246-000, BrazilDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, 05508-900, BrasilDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, 05508-900, BrasilDepartment of Pathology, A.C. Camargo Hospital, São Paulo, SP, 01509-900, BrazilDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, 05508-900, BrasilCentro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo (ICESP), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, 01246-000, BrazilCentro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo (ICESP), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, 01246-000, BrazilDepartment of Pediatrics Laboratory of Medical Investigation, School of Medicine, Universidade de São Paulo, São Paulo, SP, 01246-000, BrazilDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, 05508-900, BrasilDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, 05508-900, Brasil; Corresponding authors at: Alexandre Bruni-Cardoso and Eduardo Moraes Reis, Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, 05508-900, Brazil, Tel: +55 1130919047Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, 05508-900, Brasil; Corresponding authors at: Alexandre Bruni-Cardoso and Eduardo Moraes Reis, Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, 05508-900, Brazil, Tel: +55 1130919047Invasion 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 αV and correlation with clinical parameters. Patients with lower levels of integrin αV staining showed reduced cancer specific survival. A subset of cases presented a peripheral staining of integrin αV 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 αV at their periphery, whereas this pattern was mostly lost in invasive components, even in the same sample. The lack of peripheral integrin αV correlated with decreased cancer specific survival. In addition, we observed that the presence of integrin αV 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 αV had increased risk of developing metastasis, high co-expression of integrin αV 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 αV pattern seen in patient samples. Taken together, our data indicate that both the expression levels of integrin αV 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.http://www.sciencedirect.com/science/article/pii/S1476558622000306Breast cancerTissue microarrayIntegrin αV3D cell cultureTumor stromaMetastasis |
| spellingShingle | Otto Luiz Dutra Cerqueira Mayara Carolline Silva Botelho Ana Paula Zen Petisco Fiore Cynthia Aparecida Bueno de Toledo Osório Rebeka Tomasin Mauro César Cafundó Morais Rossana Verónica Mendoza López Elaine Cristina Cardoso Santiago Andres Vilella-Arias Eduardo Moraes Reis Alexandre Bruni-Cardoso Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas Neoplasia: An International Journal for Oncology Research Breast cancer Tissue microarray Integrin αV 3D cell culture Tumor stroma Metastasis |
| title | Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas |
| title_full | Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas |
| title_fullStr | Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas |
| title_full_unstemmed | Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas |
| title_short | Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas |
| title_sort | prognostic value of integrin αv expression and localization pattern in invasive breast carcinomas |
| topic | Breast cancer Tissue microarray Integrin αV 3D cell culture Tumor stroma Metastasis |
| url | http://www.sciencedirect.com/science/article/pii/S1476558622000306 |
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