Protein Linked to Poorer Ovarian Cancer Outcomes

Tissue transglutaminase represents ovarian carcinoma target; overexpression associated with lower survival

MONDAY, July 21 (HealthDay News) -- Overexpression of tissue type transglutaminase (TG2) in ovarian carcinoma is associated with poorer patient survival; TG2 also spurs cancer cell attachment, invasion, and resistance to chemotherapy, according to research published in the July 15 issue of Cancer Research.

Jee Young Hwang, M.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues analyzed data from several experiments assessing the significance of TG2. After evaluating TG2 expression in samples of 93 epithelial ovarian cancers, they found that overexpression was associated with high tumor stage -- overexpression was found in 69 percent of high-stage cancers compared with 30 percent of low-stage cancers -- and was a predictor of poor survival.

When the researchers inhibited TG2 in HeyA8 ovarian cancer cells with small interfering RNA (siRNA), the cells' invasive potential significantly decreased. In addition, this TG2 knockdown increased docetaxel-induced cell death. They also found antitumor benefits in mice using an siRNA delivery method called TG2 siRNA-DOPC alone or combined with docetaxel.

"In summary, targeted therapy with TG2 siRNA-DOPC in combination with chemotherapy significantly reduces tumor growth in both chemotherapy-sensitive and chemotherapy-resistant models. This antitumor effect was closely related to reduced proliferation, decreased angiogenesis, and increased tumor cell apoptosis, in addition to decreased attachment and invasion. Given the clinical relationship between TG2 and ovarian cancer prognosis, our findings raise the possibility that TG2 silencing in combination with docetaxel chemotherapy could be a novel therapeutic option against advanced ovarian carcinoma," the authors conclude.

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