Syndecan-1 alterations during the tumorigenic progression of human colonic Caco-2 cells induced by human Ha-ras or polyoma middle T oncogenes.
The products of ras and src proto-oncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study we attempted to establish whether the tumorigenic progression induced by oncogenic activation of p21ras and pp60c-src in human colonic Caco-2 cells is associated with specific alterations of syndecan-1, a membrane-anchored proteoglycan playing a role in cell-matrix interaction and neoplastic growth control. To this end, we used Caco-2 cells made highly tumorigenic by transfection with an activated (Val 12) human Ha-ras gene or with the polyoma middle T (Py-MT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. Compared with control vector-transfected Caco-2 cells, both oncogene-transfected cell lines (1) contained smaller amounts of membrane-anchored PGs; (2) exhibited decreased syndecan-1 expression at the protein but not the mRNA level; (3) synthesized 35S-labelled syndecan-1 with decreased specific activity; (4) produced a syndecan-1 ectodomain with a lower molecular mass and reduced GAG chain size and sulphation; and (5) expressed heparanase degradative activity. These results show that the dramatic activation of the tumorigenic potential induced by oncogenic p21ras or Py-MT/pp60c-src in Caco-2 cells is associated with marked alterations of syndecan-1 expression at the translational and post-translational levels.
Levy
P
P
Laboratoire de Biologie Cellulaire, INSERM-U.402, Faculté de Médecine Saint-Antoine, Paris, France.
Munier
A
A
Baron-Delage
S
S
Di Gioia
Y
Y
Gespach
C
C
Capeau
J
J
Cherqui
G
G
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D018938:Caco-2 Cells; D002809:Chondroitin Sulfates / Q000032:analysis; D011905:Genes, ras; D005966:Glucuronidase; D006026:Glycoside Hydrolases / Q000378:metabolism; D006497:Heparan Sulfate / Q000032:analysis; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D053668:Syndecan-1; D053667:Syndecans; D000099175:Heparanase
D000952:Antigens, Polyomavirus Transforming; D002809:Chondroitin Sulfates; D005966:Glucuronidase; D006026:Glycoside Hydrolases; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D016392:Proto-Oncogene Proteins pp60(c-src); D012333:RNA, Messenger; D053668:Syndecan-1; D053667:Syndecans; D000099175:Heparanase; C508241:SDC1 protein, human