The alpha 6-integrin receptor in pancreatic carcinoma.

BACKGROUND/AIMS: The alpha 6-containing integrin was suggested to be involved in the process of tumor invasion and metastasis. Therefore, the aim of the study was to investigate the expression and function of this adhesion receptor in pancreatic carcinoma.

METHODS

Integrin expression was investigated in pancreatic tissue and tumor cell lines using immunohistochemistry. Radioimmunoprecipitation was used to determine the complex composition of alpha 6. To analyze the function of the alpha 6-containing integrin in pancreatic cancer, in vitro adhesion, migration, and invasion experiments were performed.

RESULTS

The alpha 6-containing integrin was differentially expressed in normal pancreas and pancreatic carcinoma. Immunoprecipitation of different pancreatic carcinoma cell lines showed that alpha 6 was expressed together with the beta 4 subunit as alpha 6 beta 4 complex. However, adhesion of pancreatic cancer cells to laminin could be inhibited with anti-alpha 6 and anti-beta 1 integrin antibodies but not by anti-beta 4 integrin antibody. Migration of the cells through laminin was almost completely inhibited by anti-beta 1 antibody but not by other anti-integrin antibodies. Tumor cell invasion through a reconstituted basement membrane was only slightly inhibited by anti-alpha 6 antibody. In contrast, a marked inhibition was observed using anti-beta 1 antibodies, anti-alpha 2-anti-alpha 5 antibodies, and RGDS.

CONCLUSIONS

The alpha 6-containing integrin is a laminin adhesion receptor in pancreatic carcinoma cells, possibly involved in tumor invasion through the basement membrane.