Glypican-1 in human breast cancer

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...

Reexamination Certificate

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C435S004000, C435S007200, C435S007210, C435S007230, C436S063000, C436S064000, C436S086000, C436S164000, C436S174000, C436S512000, C436S536000, C424S130100, C424S138100, C530S300000, C530S350000, C530S385000, C530S386000, C530S387100, C530S387300, C530S387700, C530S387900, C530S388100, C530S391700

Reexamination Certificate

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07108986

ABSTRACT:
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.

REFERENCES:
Matsuda et al. Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells. Cancer Research 61(14): 5562-5569, Jul. 15, 2001.
Kleeff et al. The cell-surface heparin sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carinoma cells and is overexpressed in human pancreatic. J. Clin. Invest. 102(9): 1662-1673, Nov. 1, 1998.

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