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Novel role: EZH2 boosts creation of ovarian cancer blood vessels
Date:8/16/2010

or those with normal levels.

In a series of lab experiments, the team found that vascular endothelial growth factor (VEGF), a known stimulator of angiogenesis, boosts the level of EZH2 in endothelial cells. EZH2 then silences the vasohibin1 (VASH1) gene, which normally inhibits blood-vessel-formation. Silencing the EZH2 gene in the tumor's endothelial cells reactivates VASH1, reducing angiogenesis and ovarian cancer growth in mice.

Silencing ezh2 reduces tumor weight

The ezh2 gene was targeted separately in tumor cells and in endothelial cells by delivery of small interfering RNA (siRNA) - short snippets of RNA that block gene expression - to mice with one of two strains of ovarian cancer.

  • Treating mice with siRNA that silenced ezh2 in the tumor-associated endothelial cells reduced average tumor weight by 62 percent and 40 percent in the two strains of cancer compared with control mice.
  • Hitting the gene only in the tumor had little significant effect on tumor burden.
  • Silencing in both tumor and endothelial cells reduced average tumor weight by 83 percent and 65 percent in the two cancer strains.

Additional tests showed that silencing ezh2 reduced both he number of blood vessels serving the tumors and ovarian cancer cell proliferation while increasing programmed death of tumor cells.

siRNA delivery system relies on crustacean shell component

Sood and co-author Gabriel Lopez-Berestein, M.D., professor in UT MD Anderson's Department of Experimental Therapeutics, have developed delivery systems that package siRNA with a fatty ball called a liposome to silence specific genes in cancer cells.

"Those systems are quite effective for delivery to tumors and tumor cells but not as effective for delivery to tumor vasculature," Sood said. They jointly developed a new delivery system that packages siRNA into chitosan nanoparticles. Chitosan is derived from a chitin, a struc
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0655
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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