Pigment epithelium-derived factor (PEDF) inhibits progression of liver metastasis in a mouse model of uveal melanoma.

摘要

Uveal melanoma is the most common form of adult eye cancer in the United States, forming in the middle layer of the eye and originating in pigmented melanocytes. While the primary eye tumor is treatable with high success, patients often succumb to liver metastasis within 2 to 5 years. Metastatic progression is highly dependent on angiogenesis, or the formation of new blood vessels, to nourish the growing tumor with oxygen and nutrients. Pigment epithelium-derived factor (PEDF) is one of the most potent inhibitors of angiogenesis, and it is naturally produced by liver hepatocytes. I hypothesized that PEDF inhibits metastatic progression via a mechanism involving angiogenesis. I used PEDF null mice, injected melanoma cells into the posterior compartment of the eye, and measured liver metastasis after 4 weeks. PEDF null mice exhibited a 34.6-fold increase in liver metastasis area and a much greater population of macrometastases (>200 microns in diameter) when compared to controls. Vascular density was also significantly increased in these metastases, and various other characteristics were measured such as stromagenic factors and the effects of fatty liver. I concluded that PEDF is protective against metastatic progression of ocular melanoma in the liver. These findings may prove useful for future therapies.