SYNDECAN-1 ALTERATIONS DURING THE TUMORIGENIC PROGRESSION OF HUMAN COLONIC CACO-2 CELLS INDUCED BY HUMAN HA-RAS OR POLYOMA MIDDLE T-ONCOGENE

The products of ras and src proto-oncogenes are frequently activated i n a constitutive state in human colorectal cancer. In this study we at tempted to establish whether the tumorigenic progression induced by on cogenic activation of p21(ras) and pp60(c-src) in human colonic Caco-2 cells is associated with specific alterations of syndecan-1, a membra ne-anchored proteoglycan playing a role in cell-matrix interaction and neoplastic growth control. To this end, we used Caco-2 cells made hig hly tumorigenic by transfection with an activated (Val 12) human Ha-ra s gene or with the polyoma middle T (Py-MT) oncogene, a constitutive a ctivator of pp60(c-src) tyrosine kinase activity. Compared with contro l vector-transfected Caco-2 cells, both oncogene-transfected cell line s (1) contained smaller amounts of membrane-anchored PGs; (2) exhibite d decreased syndecan-1 expression at the protein but not the mRNA leve l; (3) synthesised S-35-labelled syndecan-1 with decreased specific ac tivity; (4) produced a syndecan-1 ectodomain with a lower molecular ma ss and reduced GAG chain size and sulphation; and (5) expressed hepara nase degradative activity. These results show that the dramatic activa tion of the tumorigenic potential induced by oncogenic p21(ras) or Py- MT/pp60(c-src) in Caco-2 cells is associated with marked alterations o f syndecan-1 expression at the translational and post-translational le vels.