title: Expression of thrombospondin-1 by tumor cells in patient-derived ovarian carcinoma xenografts.
abstract: OBJECTIVE
  Thrombospondin-1 (TSP-1), a major regulator of cell interaction with the environment, is often deregulated in cancers, including ovarian carcinoma. Both the tumor and the host cells can release TSP-1 in the tumor microenvironment. The relative contribution of the two sources in determining TSP-1 levels in ovarian cancer remains to be elucidated. This study was designed to investigate the expression of tumor TSP-1 in a panel of 29 patient-derived ovarian adenocarcinoma xenografts (PDX), using analytical tools specific for human (tumor-derived) rather than murine (host-derived) TSP-1.
  
  
  METHODS
  Human-specific microarray and ELISA were used to measure tumor TSP-1 expression and plasma levels.
  
  
  RESULTS
  Tumor-derived TSP-1 was heterogeneously expressed in PDX. Expression was higher in the corresponding original patient's tumor, where stroma-derived TSP-1 is also analyzed, indicating that both the tumor and the host contribute to TSP-1 production. TSP-1 was differentially expressed according to tumor grade, but not affected by p53 expression or mutational status. Findings were confirmed in an external gene expression dataset (101 patients). In a functional enrichment analysis, TSP-1 correlated with genes related to angiogenesis, cell motility, communication and shape. Plasma TSP-1, detectable in 10/11 PDX, was not associated to its expression in the tumor. The possible association of plasma TSP-1 with p53 mutations and response to chemotherapy warrants further investigation.
  
  
  CONCLUSIONS
  Ovarian carcinoma PDX are a useful tool to investigate the relative contribution of stroma and tumor cells in the production of tumor associated factors, in relation to the tumor behavior, molecular properties and response to therapy.
authors.affiliation: a Department of Oncology , Tumor Angiogenesis Unit, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Bergamo , Italy .
authors.forename: Denise
authors.initials: D
authors.lastname: Pinessi
authors.affiliation: b Fondazione Edo ed Elvo Tempia Valenta, Laboratory of Cancer Genomics , Biella , Italy , and.
authors.forename: Paola
authors.initials: P
authors.lastname: Ostano
authors.affiliation: a Department of Oncology , Tumor Angiogenesis Unit, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Bergamo , Italy .
authors.forename: Patrizia
authors.initials: P
authors.lastname: Borsotti
authors.affiliation: c Department of Oncology , IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milano , Italy.
authors.forename: Ezia
authors.initials: E
authors.lastname: Bello
authors.affiliation: c Department of Oncology , IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milano , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Guffanti
authors.affiliation: c Department of Oncology , IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milano , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bizzaro
authors.affiliation: c Department of Oncology , IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milano , Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Frapolli
authors.affiliation: c Department of Oncology , IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milano , Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Bani
authors.affiliation: b Fondazione Edo ed Elvo Tempia Valenta, Laboratory of Cancer Genomics , Biella , Italy , and.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chiorino
authors.affiliation: a Department of Oncology , Tumor Angiogenesis Unit, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Bergamo , Italy .
authors.forename: Giulia
authors.initials: G
authors.lastname: Taraboletti
authors.affiliation: a Department of Oncology , Tumor Angiogenesis Unit, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Bergamo , Italy .
authors.forename: Andrea
authors.initials: A
authors.lastname: Resovi
mesh_terms: D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D055106:Genome-Wide Association Study / Q000379:methods; D064593:Heterografts; D051379:Mice; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D019700:Thrombospondin 1; C585483:Thbs1 protein, mouse
keywords: Matricellular proteins; ovarian cancer; patient-derived xenografts; thrombospondin-1; tumor microenvironment