A protein associated with cancer progression made by tumors also unexpectedly regulates the creation of new blood vessels (angiogenesis) that feed the tumor. The new findings come from scientists at The University of Texas MD Anderson Cancer Center and were reported in the journal Cancer Cell. The protein, called EZH2, is a member of a group of molecules known to suppress the expression of genes that prevent cancer growth. EZH2 is known to be associated with the progression and spread of bladder, breast, prostate and gastric cancers and at least one type of cancer of the oral pharynx.
In the study, an examination of 180 ovarian cancer tumors discovered that EZH2 was overexpressed by the tumor in 66% of cases, as well as in tumor blood vessel cells, called endothelial cells, in 67% of samples. Increased expression of EZH2 in either the tumor or its blood vessels was associated with more advanced disease and substantially poorer survival. Patients with increased EZH2 levels in tumor endothelial cells lived about 2.33 years compared to 8.33 years for those patients whose tumors had normal levels of the protein.
Additionally, the research team found that the protein, vascular endothelial growth factor (VEGF), a critical stimulator of angiogenesis, boosts levels of EZH2 in blood vessel endothelial cells. EZH2 then suppresses the gene for vasohibin1 (VASH1), which serves as part of the body’s cancer defense system by normally inhibiting angiogenesis. When the researchers turned off the EZH2 gene, the endothelial cells reactivated VASH1, which reduced angiogenesis and decreased ovarian cancer growth in mice.
“Tumors treated with current anti-angiogenesis drugs eventually progress,” said study senior author Anil Sood, M.D., professor in UT MD Anderson’s departments of Gynecologic Oncology and Cancer Biology. “Our findings on the role of EZH2 in regulating angiogenesis opens the door for development of new treatment approaches to overcome this problem.”
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