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Oct-3/4 Expression Reflects Tumor Progression and Regulates Motility of Bladder Cancer Cells

¹ Institute of Basic Medical Sciences, ² Institute of Clinical Medicine, Departments of ³ Microbiology and Immunology and ⁴ Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan; Departments of ⁵ Urology and ⁶ Pathology, Tainan Hospital, Department of Health, Executive Yuan, Taiwan; and ⁷ Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom

Requests for reprints: Chao-Liang Wu, Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, 1 Dashiue Road, Tainan 70101, Taiwan. Phone: 886-6-2353535, ext. 5536; Fax: 886-6-2741694; E-mail: wumolbio{at}mail.ncku.edu.tw and Ai-Li Shiau, Department of Microbiology and Immunology, National Cheng Kung University Medical College, 1 Dashiue Road, Tainan 70101, Taiwan. Phone: 886-6-2353535, ext. 5629; Fax: 886-6-2363715; E-mail: alshiau{at}mail.ncku.edu.tw.

Key Words: Oct-3/4 • POU5F1 • prognostic marker • bladder cancer • oncolytic adenovirus

Cancer and embryonic stem cells exhibit similar behavior, including immortal, undifferentiated, and invasive activities. Here, we show that in clinical samples bladder tumors with intense expression of stem cell marker Oct-3/4 (also known as POU5F1) are associated with further disease progression, greater metastasis, and shorter cancer-related survival compared with those with moderate and low expressions. Expression of Oct-3/4 is detected in human bladder transitional cell carcinoma samples and cell lines. Overexpression of Oct-3/4 enhances, whereas knockdown of Oct-3/4 expression by RNA interference reduces, migration and invasion of bladder cancer cells. Oct-3/4 can up-regulate fibroblast growth factor-4 and matrix metalloproteinase-2 (MMP-2), MMP-9, and MMP-13 production, which may contribute to tumor metastasis. Finally, we show that Ad5WS4, an E1B-55 kD–deleted adenovirus driven by the Oct-3/4 promoter, exerts potent antitumor activity against bladder cancer in a syngeneic murine tumor model. Therefore, our results implicate that Oct-3/4 may be useful as a novel tumor biological and prognostic marker and probably as a potential therapeutic target for bladder cancer. [Cancer Res 2008;68(15):6281–91]

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