Integrin alpha 6 beta 1 role in metastatic behavior of human pancreatic carcinoma cells

The factors that determine the metastatic behavior of pancreatic tumor cell s are incompletely understood. In this study, we first demonstrate differen ces in adhesion properties, integrin expression and in vive integrin functi on in the metastatic tumor cell line PaTu 8988s compared with the non-metas tatic cell line PaTu 8988t. Both cell lines were derived from the same orig inal tumor and exhibit identical genetic fingerprints. Using in vitro adhes ion assays performed on purified extracellular matrix components, adhesion of PaTu 8988s cells was significantly increased on the basal membrane compo nent laminin and decreased on the interstitial matrix protein fibronectin c ompared to PaTu 8988t cells. By immunocytochemistry and flow cytometry, and in correspondence with their adhesive properties, the metastatic PaTu 8988 s cells did express a distinct pattern of integrin subunits. Laminin-bindin g integrins alpha 6 and beta 4 were overexpressed in PaTu 8988s cells. Fibr onectin-binding alpha 5 integrins were present at higher levels in the non- metastatic PaTu 8988t cells, whereas the beta 1 subunit expression did not differ, Adhesion to laminin or fibronectin was specific and was mediated vi a integrins alpha 6 beta 1 and alpha 5 beta 1, respectively. In addition, m etastasis formation in vive after injection of cells into the tail vein of nude mice was inhibited by preincubation of PaTu 8988s cells with antibodie s directed against the integrin alpha 6 or beta 1,we conclude that alpha 6 beta 1 integrins are overexpressed and functionally active in metastatic hu man pancreatic carcinoma cells, and participate in metastasis formation pro bably through binding to the basal membrane component laminin, Int. J, Canc er 80:791-795, 1999, (C) 1999 Wiley-Liss, Inc.