J Cancer 2017; 8(7):1137-1144. doi:10.7150/jca.18297 This issue

Research Paper

Impact of CD44 expression on radiation response for bladder cancer

Chun-Te Wu1, 2, Wei-Yu Lin2, 3, Ying-Hsu Chang4, Wen-Cheng Chen2, 5, Miao-Fen Chen2, 5✉

1. Department of Urology, Chang Gung Memorial Hospital at Keelung, Taiwan;
2. Chang Gung University, College of Medicine, Taoyuan, Taiwan;
3. Department of Urology, Chang Gung Memorial Hospital at Chiayi, Taiwan;
4. Department of Urology, Chang Gung Memorial Hospital at Linko, Taiwan.
5. Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan;

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Wu CT, Lin WY, Chang YH, Chen WC, Chen MF. Impact of CD44 expression on radiation response for bladder cancer. J Cancer 2017; 8(7):1137-1144. doi:10.7150/jca.18297. Available from https://www.jcancer.org/v08p1137.htm

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Background Identification of potential factors that can stratify tumors' response to specific therapies will aid in the selection of cancer therapy. Radioresistance is the major obstacles to positive outcomes in bladder cancer patients after definite chemotherapy. CD44, a cancer stem cell surface marker, is relevant in treatment resistance. In the present study, we examined the role of CD44 in bladder cancer.

Methods We retrospectively analyzed the clinical outcomes of 85 bladder cancer patients treated with definite chemoradiotherapy, and correlated the expressions of CD44 with IL-6 and treatment response. Furthermore, the bladder cancer cell lines HT1197 and MB49 were selected for cellular and animal experiments to investigate the links between the CD44, IL-6 and radiation response.

Results Analyzing the clinical specimen, the staining of CD44 was significantly linked with higher clinical stage, lower complete response rates, higher loco-regional failure rate and lower survival rate with intact bladder for patients treated with definite CCRT. In addition, the frequency of CD44 immunoreactivity was significantly higher in IL-6-positive bladder cancer specimens. By cellular experiments, the expression of CD44 was stimulated by IL-6 and linked with the cancer stem cell-like property. As demonstrated through in vitro and animal experiments using immunocompromised and immunocompetent hosts, CD44+ bladder cancer cells appeared more resistant to irradiation, associated with less RT-induced cell death.

Conclusions Our findings suggested that CD44 is important in predicting the radiation response of bladder tumor cells. If overexpressed CD44 and/or IL-6 were noted in pre-surgical specimens, radical cystectomy is more likely to be preferred.

Keywords: CD44, radiation response, cancer stem cells, bladder cancer.