Affiliations: Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la UB, Universitat de Barcelona, Barcelona, Spain | Laboratori de Bioinvestigació, Merck Farma i Química, Barcelona, Spain
Note: [] Present address: Leitat Technological Center, Biomed Division.
Note: [] Corresponding author: Dr. Adela Mazo, Departament de Bioquímica i Biología Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain. Tel.: +34 934021210; Fax: +34 934021559; E-mail: [email protected].
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 β3 in pancreatic cancer by generating two stable β3-expressing pancreatic human cell lines and characterizing their behavior in vitro and in vivo. Results: Transduction of β3 selectively augmented the functional membrane αvβ3 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 β3-overexpressing cells. Moreover, tumors expressing β3 displayed reduced growth. Interestingly, treatment of mice with an αv-blocking antibody inhibited the growth of β3-expressing tumors to a higher extent. Conclusions: Our results collectively support the hypothesis that αvβ3 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.
