Researchers led by Drs. Elena Deryugina and James Quigley of The Scripts Research Institute in La Jolla, CA have found that urokine plasminogen activator (uPA) may be instrumental in the early stages of metastasis. Prostate cancer, which develops most frequently in men over fifty, is the most common type of cancer of men in the United States. Most prostate cancer-related deaths are due to advanced disease, which often results in metastatic spread to other organs.
Tumor cell intravasation, the entry of aggressive cells into the blood vessels, is an early step in the complex metastatic process. To explore the mechanisms governing intravasation, Conn et al isolated high and low dissemination variants of a prostate carcinoma cell line. The cell line more prone to dissemination had increased angiogenic potential, and these cells were more migratory and invasive. Highly metastatic cells also produced more of the serine protease uPA. By inhibiting uPA activation, invasion, angiogenesis, and intravasation were all blocked.
Drs. Deryugina, Quigley, and colleagues conclude that "a comparative analysis of these congenic variants has indicated important functional roles for VEGF secretion and uPA activation in facilitating tumor cell intravasation and has indicated a potential direct link between tumor-induced angiogenesis and tumor cell intravasation."
- Conn et al. Comparative Analysis of Metastasis Variants Derived from Human Prostate Carcinoma Cells: Roles in Intravasation of VEGF-Mediated Angiogenesis and uPA-Mediated Invasion. American Journal Of Pathology, 2009; 175 (4): 1638 DOI: 10.2353/ajpath.2009.090384
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