Decrease of human pancreatic cancer cell tumorigenicity by α1,3galactosyltransferase gene transfer

Abstract

The enzyme α1,3galactosyltransferase synthesizes the αGal epitope, a carbohydrate structure (Galα1,3Galβ1,4GlcNAc-R), on glycoconjugates in lower mammals. The enzyme is absent in humans but large amounts of natural antibodies that recognize αGal epitopes are present in human serum. It is likely that these antibodies contribute to the host defense and participate in the hyperacute rejection of xenograft. Previous studies indicated that the glycosyltransferase gene transfer into tumoral cells can modify the structure of glycoconjugates at the cell surface and, as a consequence, modulates the metastatic and tumorigenic behaviors of these cells. The aim of our study was to determine whether the expression of αGal epitope can modify the tumorigenicity of human pancreatic cancer cells. The expression of αGal epitopes in the human pancreatic cancer cell lines BxPC-3 and Panc-1 was obtained by selecting stable cell clones transfected with murine α1,3galactosyltransferase gene. The expression of the enzyme activity in BxPC-3 and Panc-1 cells resulted in the formation at the cell surface of αGal epitopes that are recognized by human anti-αGal antibodies. αGal epitope expression at the surface of pancreatic cancer cells was associated with the fixation of complement 1q to human anti-αGal antibodies. The αGal epitope expression also resulted in a delay in the tumoral development of BxPC-3 and Panc-1 cells in vivo after xenograft transplantation of nude mice. In addition to the impairment of the metastatic potential of murine tumor cell lines and the activation of immune response, our study provides evidence that the cell surface expression of αGal epitopes also modulates the tumorigenic behavior of human pancreatic cancer cells. © 2003 Wiley-Liss, Inc.