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Tumor Biology

Elevated Levels of Syndecan-1 Expression Confer Potent Serum-dependent Growth in Human 293T Cells

Fumitaka Numa, Kei Hirabashi, Nagato Tsunaga, Hiroshi Kato, Karen O'Rourke, Shao Haining, Connie Stechmann-Lebakken, James Varani, Alan Rapraeger and Vishva M. Dixit
Fumitaka Numa
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Kei Hirabashi
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Nagato Tsunaga
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Hiroshi Kato
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Karen O'Rourke
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Shao Haining
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Connie Stechmann-Lebakken
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James Varani
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Alan Rapraeger
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Vishva M. Dixit
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DOI:  Published October 1995
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Abstract

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 Eia 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.

Footnotes

  • ↵1 To whom requests for reprints should be addressed.

    • ©1995 American Association for Cancer Research.
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    October 1995
    Volume 55, Issue 20
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    Elevated Levels of Syndecan-1 Expression Confer Potent Serum-dependent Growth in Human 293T Cells
    Fumitaka Numa, Kei Hirabashi, Nagato Tsunaga, Hiroshi Kato, Karen O'Rourke, Shao Haining, Connie Stechmann-Lebakken, James Varani, Alan Rapraeger and Vishva M. Dixit
    Cancer Res October 15 1995 (55) (20) 4676-4680;

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    Elevated Levels of Syndecan-1 Expression Confer Potent Serum-dependent Growth in Human 293T Cells
    Fumitaka Numa, Kei Hirabashi, Nagato Tsunaga, Hiroshi Kato, Karen O'Rourke, Shao Haining, Connie Stechmann-Lebakken, James Varani, Alan Rapraeger and Vishva M. Dixit
    Cancer Res October 15 1995 (55) (20) 4676-4680;
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