Oct-3/4 expression reflects tumor progression and regulates motility of bladder cancer cells
Oct-3/4 expression reflects tumor progression and regulates motility of bladder cancer cells
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DOI：
10.1158/0008-5472.can-08-0094
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发表时间：
2008-08-01
期刊：
影响因子：
11.2
通讯作者：
Wu, Chao-Liang
中科院分区：
文献类型：
--
作者：
Chang, Chao-Ching;Shieh, Gia-Shing;Wu, Chao-Liang
癌症和胚胎干细胞表现出类似的行为，包括永生，未分化和侵入性活动。在这里，我们发现，在临床样本中，干细胞标志物Oct-3/4（也称为POU 5 F1）强烈表达的膀胱肿瘤与中度和低度表达的膀胱肿瘤相比，与进一步的疾病进展，更大的转移和更短的癌症相关生存期相关。在人膀胱移行细胞癌样品和细胞系中检测到Oct-3/4的表达。Oct-3/4的过表达增强膀胱癌细胞的迁移和侵袭，而通过RNA干扰敲低Oct-3/4的表达降低膀胱癌细胞的迁移和侵袭。Oct-3/4可上调成纤维细胞生长因子-4和基质金属蛋白酶-2（MMP-2）、MMP-9和MMP-13的产生，这可能有助于肿瘤转移。最后，我们表明，Ad 5 WS 4，E1 B-55 kD缺失的腺病毒驱动的Oct-3/4启动子，发挥有效的抗肿瘤活性，对膀胱癌的同基因小鼠肿瘤模型。因此，我们的研究结果表明，Oct-3/4可能是一种新的肿瘤生物学和预后标志物，并可能作为膀胱癌的潜在治疗靶点。
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.