Glypicans in growth control and cancer

The name glypican has been assigned to a family of heparan sulfate (HS) pro teoglycans that are linked to the cell membrane by a glycosyl-phosphatidyli nositol anchor. To date, six family members of this family have been identi fied in mammals (GPC1 to GPC6) and two in Drosophila. Glypicans are express ed predominantly during development, and they are thought to play a role in morphogenesis. As HS-carrying molecules, glypicans were initially consider ed potential regulators of heparin-binding growth factors. This has been re cently confirmed by genetic interaction experiments showing that glypicans regulate wingless signaling in Drosophila. The involvement of glypicans in the in vivo regulation of other heparin-binding growth factors, such as fib roblast growth factors, remains to be determined. Interestingly and unexpec tedly, a role for GPC3 in the regulation of insulin-like growth factors has been proposed. This hypothesis is based on the phenotype of patients with Simpson-Golabi-Behmel syndrome (SGBS), an overgrowth and dysmorphic syndrom e in which the GPC3 gene is mutated. Thus, it is possible that glypicans re gulate different kinds of growth factors in a tissue-specific manner. In ad dition to its involvement in SGBS, down-regulation of GPC3 has been recentl y associated with the progression of several types of malignant tumors, inc luding mesotheliomas and ovarian cancer. A role for GPC1 in pancreatic canc er progression has also been proposed.