Oct-3/4 expression reflects tumor progression and regulates motility of bladder cancer cells.
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.
Chang
Chao-Ching
CC
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
Shieh
Gia-Shing
GS
Wu
Pensee
P
Lin
Chia-Cheng
CC
Shiau
Ai-Li
AL
Wu
Chao-Liang
CL
D000818:Animals; D018450:Disease Progression; D051519:Fibroblast Growth Factor 4 / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D020782:Matrix Metalloproteinases