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 func tions to modulate epithelial cell attachment and physiology. Extracell ularly, syndecan-1 binds both growth factors and extracellular matrix components, and intracellularly, its cytoplasmic portion interacts wit h cytoskeletal components, To investigate the possible role of syndeca n-1 in epithelial cell transformation that is characterized by alterat ion in extracellular matrix interactions and cytoskeleton architecture , we established stable transfectants of syndecan-1 in a highly transf ormed human renal epithelial line expressing two viral oncogenes, aden ovirus E1a and SV40 large T antigen (293T cell line). Expression of sy ndecan-1 core protein and appropriate posttranslational attachment of glycosaminoglycan chains was confirmed by enzymatic digestion and West ern blot analysis, Overexpresser cells gem at a significantly faster r ate than the vector-transfected control cells in serum-rich media but showed a proliferative disadvantage in serum-reduced media, In additio n to this serum dependency, syndecan-1 overexpression caused a partial reversal of the transformed phenotype with the expressing clones beco ming more anchorage dependent and less motile than the vector-transfec ted counterparts, Surprisingly, the overexpressers were more tumorigen ic when injected s.c. into nude mice. These results indicate that synd ecan-1 expression plays a role in the control of cell proliferation an d suggest that serum-dependent growth may be the more reflective of tu morigenicity in nude mice.