Modulation of Cell Growth and Growth Factor Signaling Through Removal of Glypicans

Background: Membrane associated heparin sulfate proteoglycans (HSPGs) have been shown to play important roles in many aspects of cell behavior, including cell-cell and cell-extracellular matrix adhesion and growth factor signaling. Glypicans, members of the HSPGs, are a family of polypeptides that appear to carry the majority of the heparin sulfate on mammalian cells. These glypicans are attached to the plasma membrane via glycosylphophatidylinositol (GPI) anchors. Technology: Glycosylphosphatidylinositol-(GPI-) anchored HSPG glypican-1 (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. Expression of glypican-1 is low in normal pancreas and breast tissue. Pancreatic cancer cell lines that express glypican-1 were treated with the enzyme phosphinositide-specific phospholipase-C (PI-PLC) which enzymatically removes glypicans from the cell surface by cleaving the GPI anchors. This treatment resulted in the abrogation of the cells' mitogenic response to two heparin-binding growth factors. Treatment of breast cancer cell lines also abrogated their response to two different heparin-binding growth factors. Application: Glypican-1 can be used for the diagnosis and screening for the occurrence of breast and pancreatic cancer. Glypican-1 can also be targeted with small molecules and biologics to retard the growth of glypican-responsive cancers.

Type of Offer: Licensing



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