title: Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer.
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.
authors.affiliation: Department of Cell and Developmental Biology, Biomedical Sciences Institute, Sx00E3;o Paulo, Brazil.
authors.forename: Maíra Assis
authors.initials: MA
authors.lastname: Lima
authors.forename: Liliane
authors.initials: L
authors.lastname: Dos Santos
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Turri
authors.forename: Suely
authors.initials: S
authors.lastname: Nonogaki
authors.forename: Marcilei
authors.initials: M
authors.lastname: Buim
authors.forename: Joema Felipe
authors.initials: JF
authors.lastname: Lima
authors.forename: João
authors.initials: J
authors.lastname: de Jesus Viana Pinheiro
authors.forename: Cynthia Aparecida
authors.initials: CA
authors.lastname: Bueno de Toledo Osório
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: Vanessa Morais
authors.initials: VM
authors.lastname: Freitas
mesh_terms: D000071097:ADAMTS1 Protein / Q000378:metabolism*; D000071121:ADAMTS4 Protein / Q000378:metabolism*; D000071116:ADAMTS5 Protein / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human