Glycosylphosphatidylinositol-(GPI-) anchored HSPG glypican-1 is strongly
expressed in human breast and pancreatic cancer--both by the cancer cells
and in the case of pancreatic cancer the adjacent fibroblasts--whereas
expression of glypican-1 is low in the normal pancreas and in chronic
pancreatitis. Treatment of two pancreatic cancer cell lines, which
express glypican-1, with the enzyme phosphoinositide-specific
phospholipase-C (PI-PLC) abrogated their mitogenic responses to two
heparin-binding growth factors: fibroblast growth factor-2 (FGF2) and
heparin-binding EGF-like growth factor (HB-EGF). Treatment of MDA-MB-231
and MDA-MB-468 breast cancer cells with PI-PLC abrogates the mitogenic
response to two heparin-binding growth factors, heparin-binding epidermal
growth factor-like growth factor (HB-EGF) and fibroblast growth factor-2
(FGF-2). Syndecan-1 is also expressed at high levels in breast cancer
tissues as well as breast cancer cells by comparison with breast normal
tissues. Temporary or permanent transfection of a glypican-1 antisense
construct attenuated glypican-1 protein levels and the mitogenic response
to FGF2 and HB-EGF. Glypican can be used to detect the carcinoma in vitro
and therapeutics that either bind to (e.g., antibodies or drugs), remove
(e.g., enzymes) or prevent the expression (e.g., antisense constructs) of
surface of the extracellular domain of glypican-1 are effective in
retarding the growth of glypican-responsive carcinomas.