Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer
Pathobiology
; 83(6): 316-326, 2016.
Artigo
em Inglês
| LILACS, Sec. Est. Saúde SP
| ID: biblio-1024773
Biblioteca responsável:
BR91.2
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.
Texto completo:
Disponível
Coleções:
Bases de dados nacionais
/
Brasil
Base de dados:
LILACS
/
Sec. Est. Saúde SP
Assunto principal:
Neoplasias Ovarianas
/
Humanos
/
Biomarcadores Tumorais
/
Regulação Neoplásica da Expressão Gênica
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Neoplasias Epiteliais e Glandulares
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Inibidor Tecidual de Metaloproteinase-3
/
Proteína ADAMTS1
/
Proteína ADAMTS4
/
Carcinoma Epitelial do Ovário
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Revista:
Pathobiology
Ano de publicação:
2016
Tipo de documento:
Artigo
Instituição/País de afiliação:
Camargo Cancer Center/BR
/
Ontario Institute of Cancer Research/CA
/
Universidade Federal do Pará/BR
/
Universidade de São Paulo/BR