title: Expression of αV-integrins in uterine serous papillary carcinomas; implications for targeted therapy with intetumumab (CNTO 95), a fully human antagonist anti-αV-integrin antibody.
abstract: OBJECTIVE
  Uterine serous papillary carcinoma (USPC) is an aggressive variant of endometrial cancer characterized by an innate resistance to chemotherapy and poor prognosis. In this study, we evaluated the expression of αV-integrins in primary USPC cell lines and the in vitro ability of intetumumab (CNTO 95), a fully human monoclonal antibody against αV-integrins, to inhibit USPC cell adhesion and migration.
  
  
  METHODS
  The surface expression of integrins belonging to the αV-family, including αVβ3, αVβ5, and αVβ6, was evaluated in 6 primary USPC cell lines using flow cytometry analysis. To test the ability of intetumumab to inhibit USPC cell adhesion and migration, adhesion assays in the presence of vitronectin and migration assays through an 8.0-μm pore polycarbonate membrane also were performed.
  
  
  RESULTS
  We found high expression of the αV-subunit on the cell surface of all 6 primary USPC cell lines tested (100% positive cells; mean fluorescence intensity range, 13.1-39.5). When the expression of single heterodimeric integrins was evaluated, αVβ3, αVβ5, and αVβ6 were expressed on 37.5%, 32.0%, and 16.3% of cells (mean fluorescence intensity range, 6.5-16.2, 9.2-32.5, and 6.2-11.5, respectively). Importantly, in functional assays, low doses of intetumumab were effective in inhibiting adhesion (0.15 μg/mL, P = 0.003) and migration (1.25 μg/mL P = 0.02) of primary USPC cell lines.
  
  
  CONCLUSIONS
  The αV-integrins are overexpressed on the cell surface of primary USPC cell lines. Intetumumab may significantly inhibit USPC cell adhesion and migration pathways and may therefore represent a novel treatment option for patients harboring this rare but highly aggressive variant of endometrial cancer.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Bellone
authors.forename: Emiliano
authors.initials: E
authors.lastname: Cocco
authors.forename: Joyce
authors.initials: J
authors.lastname: Varughese
authors.forename: Stefania
authors.initials: S
authors.lastname: Bellone
authors.forename: Paola
authors.initials: P
authors.lastname: Todeschini
authors.forename: Karim
authors.initials: K
authors.lastname: El-Sahwi
authors.forename: Luisa
authors.initials: L
authors.lastname: Carrara
authors.forename: Federica
authors.initials: F
authors.lastname: Guzzo
authors.forename: Peter E
authors.initials: PE
authors.lastname: Schwartz
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rutherford
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Marshall
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D045744:Cell Line, Tumor / Q000378:metabolism; D018283:Cystadenocarcinoma, Papillary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D039564:Integrin alphaV; C486839:intetumumab