Integrin α6β1 role in metastatic behavior of human pancreatic carcinoma cells

✍ Scribed by Roger Vogelmann; Ernst D. Kreuser; Guido Adler; Manfred P. Lutz

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 82 KB
• Volume: 80
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990301)80:5<791::aid-ijc25>3.0.co;2-4

✦ Synopsis

The factors that determine the metastatic behavior of pancreatic tumor cells are incompletely understood. In this study, we first demonstrate differences in adhesion properties, integrin expression and in vivo integrin function in the metastatic tumor cell line PaTu 8988s compared with the non-metastatic cell line PaTu 8988t. Both cell lines were derived from the same original tumor and exhibit identical genetic fingerprints. Using in vitro adhesion assays performed on purified extracellular matrix components, adhesion of PaTu 8988s cells was significantly increased on the basal membrane component laminin and decreased on the interstitial matrix protein fibronectin compared to PaTu 8988t cells. By immunocytochemistry and flow cytometry, and in correspondence with their adhesive properties, the metastatic PaTu 8988s cells did express a distinct pattern of integrin subunits. Laminin-binding integrins ␣6 and ␤4 were overexpressed in PaTu 8988s cells. Fibronectin-binding ␣5 integrins were present at higher levels in the non-metastatic PaTu 8988t cells, whereas the ␤1 subunit expression did not differ. Adhesion to laminin or fibronectin was specific and was mediated via integrins ␣6␤1 and ␣5␤1, respectively. In addition, metastasis formation in vivo after injection of cells into the tail vein of nude mice was inhibited by preincubation of PaTu 8988s cells with antibodies directed against the integrin ␣6 or ␤1. We conclude that ␣6␤1 integrins are overexpressed and functionally active in metastatic human pancreatic carcinoma cells, and participate in metastasis formation probably through binding to the basal membrane component laminin.