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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer

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Author(s):
Lima, Maira Assis ; dos Santos, Liliane ; Turri, Jose Antonio ; Nonogaki, Suely ; Buim, Marcilei ; Lima, Joema Felipe ; Viana Pinheiro, Joao de Jesus ; Bueno de Toledo Osorio, Cynthia Aparecida ; Soares, Fernando Augusto ; Freitas, Vanessa Morals
Total Authors: 10
Document type: Journal article
Source: PATHOBIOLOGY; v. 83, n. 6, p. 316-326, 2016.
Web of Science Citations: 6
Abstract

Background: ADAMTS are metalloproteases with disintegrin and thrombospondin motifs. They are secreted proteases playing a role in biological processes such as inflammation, angiogenesis, and urogenital development. ADAMTS have specific substrates, such as the proteoglycans (PG) versican, aggrecan, and brevican. Despite data indicating a role of ADAMTS in tumor invasion and metastases, effects played by these molecules in cancer progression are still controversial. In ovarian cancer, the importance of ADAMTS gene mutations was recently described and related to chemotherapy outcome. Objective: To analyze protein levels of ADAMTS-1, -4, and -5, and TIMP-3 in human ovarian cancer classified as benign, borderline, or malignant. We also assessed the expression of the ADAMTS substrates aggrecan, brevican, and versican in these neoplasms. Correlations between overall survival and protein expression were performed. Methods: Tumors were classified according to the WHO Classification of Tumors of Female Reproductive Organs. Protein and PG expression was studied by immunohistochemistry. Differences in labeling were analyzed by percent measurements of stained areas. Results: ADAMTS-1, ADAMTS-5, and its tissue inhibitor TIMP-3 are increased in borderline and malignant tumors compared to benign neoplasms. Aggrecan and versican levels were increased in malignant subtypes compared to benign ovarian cancer. Higher ADAMTS-1, TIMP-3, and versican expression was associated with a shorter overall survival. Conclusions: Comparison of protease, TIMP-3, and substrate expression showed that in malignant tumors all ADAMTS and TIMP-3 expression levels were significantly raised compared to the substrates studied. (C) 2016 S. Karger AG, Basel (AU)

FAPESP's process: 10/07699-1 - Protease ADAMTS1 influencing breast cancer behavior and microenvironment
Grantee:Vanessa Morais Freitas
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 13/01092-6 - Influence of steroid hormones in expression levels and location of ADAMTS-1, 4 and 9 in cells derived from ovarian tumors
Grantee:Maíra de Assis Lima
Support type: Scholarships in Brazil - Master