title: Dual effects of β3 integrin subunit expression on human pancreatic cancer models.
abstract: BACKGROUND
  Pancreatic cancer, the fifth leading cause of adult cancer death in Western countries, lacks early detection, and displays significant dissemination ability. Accumulating evidence shows that integrin-mediated cell attachment to the extracellular matrix induces phenotypes and signaling pathways that regulate tumor cell growth and migration.
  
  
  METHODS
  In view of these findings, we examined the role of β(3) in pancreatic cancer by generating two stable β(3)-expressing pancreatic human cell lines and characterizing their behavior in vitro and in vivo.
  
  
  RESULTS
  Transduction of β(3) selectively augmented the functional membrane α(v)β(3) integrin levels, as evident from the enhanced adhesion and migration abilities related to active Rho GTPases. No effects on in vitro anchorage-dependent growth, but higher anoikis were detected in β(3)-overexpressing cells. Moreover, tumors expressing β(3) displayed reduced growth. Interestingly, treatment of mice with an α(v)-blocking antibody inhibited the growth of β(3)-expressing tumors to a higher extent.
  
  
  CONCLUSIONS
  Our results collectively support the hypothesis that α(v)β(3) integrin has dual actions depending on the cell environment, and provide additional evidence on the role of integrins in pancreatic cancer, which should eventually aid in improving prediction of the effects of therapies addressed to modulate integrin activities in these tumors.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la UB, Universitat de Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Marchán
authors.forename: S
authors.initials: S
authors.lastname: Pérez-Torras
authors.forename: A
authors.initials: A
authors.lastname: Vidal
authors.forename: J
authors.initials: J
authors.lastname: Adan
authors.forename: F
authors.initials: F
authors.lastname: Mitjans
authors.forename: N
authors.initials: N
authors.lastname: Carbó
authors.forename: A
authors.initials: A
authors.lastname: Mazo
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D051379:Mice; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D021122:Protein Subunits / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000906:Antibodies; C061248:ITGB3 protein, human; D039661:Integrin beta3; D021122:Protein Subunits; D020741:rho GTP-Binding Proteins