Elevated levels of syndecan-1 expression confer potent serum-dependent growth in human 293T cells.
Syndecan-1 is the best studied integral membrane proteoglycan and functions to modulate epithelial cell attachment and physiology. Extracellularly, syndecan-1 binds both growth factors and extracellular matrix components, and intracellularly, its cytoplasmic portion interacts with cytoskeletal components. To investigate the possible role of syndecan-1 in epithelial cell transformation that is characterized by alteration in extracellular matrix interactions and cytoskeleton architecture, we established stable transfectants of syndecan-1 in a highly transformed human renal epithelial line expressing two viral oncogenes, adenovirus E1a and SV40 large T antigen (293T cell line). Expression of syndecan-1 core protein and appropriate posttranslational attachment of glycosaminoglycan chains was confirmed by enzymatic digestion and Western blot analysis. Overexpresser cells grew at a significantly faster rate than the vector-transfected control cells in serum-rich media but showed a proliferative disadvantage in serum-reduced media. In addition to this serum dependency, syndecan-1 overexpression caused a partial reversal of the transformed phenotype with the expressing clones becoming more anchorage dependent and less motile than the vector-transfected counterparts. Surprisingly, the overexpressers were more tumorigenic when injected s.c. into nude mice. These results indicate that syndecan-1 expression plays a role in the control of cell proliferation and suggest that serum-dependent growth may be the more reflective of tumorigenicity in nude mice.
Numa
F
F
Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Ube, Japan.
Hirabayashi
K
K
Tsunaga
N
N
Kato
H
H
O'Rourke
K
K
Shao
H
H
Stechmann-Lebakken
C
C
Varani
J
J
Rapraeger
A
A
Dixit
V M
VM
D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D003470:Culture Media; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D053668:Syndecan-1; D053667:Syndecans; D014162:Transfection; D014407:Tumor Cells, Cultured
D003470:Culture Media; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans