Discovery of a Novel Molecule that Regulates Tumor Growth and Metastasis

The heparan sulfate proteoglycan, Glypican-1 (GPC1), significantly impacts the growth of pancreatic cancer cells in vivo and markedly attenuates tumor angiogenesis and metastasis in athymic mice. Interestingly, both cancer cell-derived and host-derived GPC1 play an important role in tumor development and spread. These data suggest that GPC1 may be a valid therapeutic target for pancreatic cancer. KEYWORDS: Glypican-1, GPC1, pancreatic cancer, PDAC, angiogenesis, metastasis, tumor growth, microenvironment Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic and biologically aggressive malignancy that is the fourth leading cause of cancer death in the U.S. with a 5-year survival rate of less than 5%. Since PDAC is usually diagnosed at an advanced stage, after the tumor has already metastasized and is no longer operable, the number of new PDAC cases diagnosed each year is nearly equivalent to the mortality rate In a recent study published in the Journal of Clinical Investigation, it was shown that a common growth factor coreceptor, Glypican-1 (GPC1), is abnormally abundant in pancreatic cancer and that the loss of GPC1 results in reduced tumor growth, angiogenesis, and metastasi

Discovery of a Novel Molecule that Regulates Tumor Growth and Metastasis

The heparan sulfate proteoglycan, Glypican-1 (GPC1), significantly impacts the growth of pancreatic cancer cells in vivo and markedly attenuates tumor angiogenesis and metastasis in athymic mice. Interestingly, both cancer cell-derived and host-derived GPC1 play an important role in tumor development and spread. These data suggest that GPC1 may be a valid therapeutic target for pancreatic cancer

Discovery of a Novel Molecule that Regulates Tumor Growth and Metastasis

The heparan sulfate proteoglycan, Glypican-1 (GPC1), significantly impacts the growth of pancreatic cancer cells in vivo and markedly attenuates tumor angiogenesis and metastasis in athymic mice. Interestingly, both cancer cell-derived and host-derived GPC1 play an important role in tumor development and spread. These data suggest that GPC1 may be a valid therapeutic target for pancreatic cancer

Glypican-1 modulates the angiogenic and metastatic potential of human and mouse cancer cells.

Cells isolated from many types of human cancers express heparin-binding growth factors (HBGFs) that drive tumor growth, metastasis, and angiogenesis. The heparan sulfate proteoglycan glypican-1 (GPC1) is a coreceptor for HBGFs. Here we show that both cancer cell-derived and host-derived GPC1 are crucial for efficient growth, metastasis, and angiogenesis of human and mouse cancer cells. Thus downregulation of GPC1 in the human pancreatic cancer cell line PANC-1, using antisense approaches, resulted in prolonged doubling times and decreased anchorage-independent growth in vitro as well as attenuated tumor growth, angiogenesis, and metastasis when these cells were transplanted into athymic mice. Moreover, athymic mice that lacked GPC1 exhibited decreased tumor angiogenesis and metastasis following intrapancreatic implantation with either PANC-1 or T3M4 human pancreatic cancer cells and fewer pulmonary metastases following intravenous injection of murine B16-F10 melanoma cells. In addition, hepatic endothelial cells isolated from these mice exhibited an attenuated mitogenic response to VEGF-A. These data indicate that cancer cell- and host-derived GPC1 are crucial for full mitogenic, angiogenic, and metastatic potential of cancer cells. Thus targeting GPC1 might provide new avenues for cancer therapy and for the prevention of cancer metastasis

Glypican-1 modulates the angiogenic and metastatic potential of human and mouse cancer cells

Cells isolated from many types of human cancers express heparin-binding growth factors (HBGFs) that drive tumor growth, metastasis, and angiogenesis. The heparan sulfate proteoglycan glypican-1 (GPC1) is a coreceptor for HBGFs. Here we show that both cancer cell–derived and host-derived GPC1 are crucial for efficient growth, metastasis, and angiogenesis of human and mouse cancer cells. Thus downregulation of GPC1 in the human pancreatic cancer cell line PANC-1, using antisense approaches, resulted in prolonged doubling times and decreased anchorage-independent growth in vitro as well as attenuated tumor growth, angiogenesis, and metastasis when these cells were transplanted into athymic mice. Moreover, athymic mice that lacked GPC1 exhibited decreased tumor angiogenesis and metastasis following intrapancreatic implantation with either PANC-1 or T3M4 human pancreatic cancer cells and fewer pulmonary metastases following intravenous injection of murine B16-F10 melanoma cells. In addition, hepatic endothelial cells isolated from these mice exhibited an attenuated mitogenic response to VEGF-A. These data indicate that cancer cell– and host-derived GPC1 are crucial for full mitogenic, angiogenic, and metastatic potential of cancer cells. Thus targeting GPC1 might provide new avenues for cancer therapy and for the prevention of cancer metastasis