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Dartmouth Team Isolates Molecule that Facilitates Cancer Spread

January 7, 2008

The discovery by a Dartmouth Medical School (DMS) team that a specific molecule drives local tumor growth, as well as its ability to flourish and spread, opens a new window for understanding and treating cancer by taking aim at both cancer cells and their surrounding environment.

The team, led by Dr. Murray Korc, MD, found that a member of a common molecular family plays a role in the progress of a particularly resilient and aggressive pancreatic cancer, and that its influence is not restricted to that cancer. Their research was reported in the January Journal of Clinical Investigation.

Korc is Chair of the Department of Medicine at Dartmouth-Hitchcock Medical Center and Professor of Medicine and of Pharmacology & Toxicology at Dartmouth Medical School. Co-authors on the research are Takuma Aikawa, Chery A. Whipple, Jason Gunn, Alison Young, of DMS, and Martha E. Lopez and Arthur D. Lander of the University of California, Irvine.

The work builds on studies by Korc, and colleagues at UC Irvine, on glypican molecules, which interact with many growth factors implicated in cancer. A receptor called glypican-1 (GPC1) is abnormally abundant in pancreatic ductal adenocarcinoma, the most common and deadliest form of pancreatic cancer, often diagnosed after it has spread or metastasized. Human pancreatic cells deprived of their own GPC1 had reduced growth in culture, as well as when they were transplanted into immunocompromised mice (known as athymic for the lack of a thymus gland) that don't reject human cancer cells, the researchers demonstrated.

"Tumors grow more slowly and are smaller. Interestingly, they also have less angiogenesis (blood vessel growth) and less metastasis," Korc said.

Since GPC1 is common in many tissues, the researchers wanted to determine its role in the host environment. Knocking out the gene for GPC1 in mice, they created an athymic mouse population that lacked GPC1; then they introduced cancer cells. Host mice devoid of GPC1 had smaller pancreatic tumors that were less angiogenic and less metastatic when exposed to tumor cell lines with normal levels of GPC1. The metastatic potential of mouse melanoma (skin cancer) cells injected into mice with no GPC1 was also greatly decreased, the researchers found.

"We've shown that GPC1 in the cancer cells and in the host - that is, the patient - is important not only for tumor growth, but for tumor angiogenesis and metastasis, Korc said. "This raises the possibility for therapeutic manipulations that will target GPC1 in both cancer cells and in patients to slow tumor growth and to prevent metastasis."

Zeroing in on mechanisms that allow metastasis to occur more efficiently - namely, the presence of GPC1- in either the cancer cells or the host, offers new options against cancer. The approach seems promising because, added Korc, "Host-cancer interactions are becoming significant as clinicians and cancer researchers realize that the environment around cancer cells is just as important as the cancer cells themselves."