Periostin is down-regulated in high grade human bladder cancers and suppresses in vitro cell invasiveness and in vivo metastasis of cancer cells
Periostin is down-regulated in high grade human bladder cancers and suppresses in vitro cell invasiveness and in vivo metastasis of cancer cells
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DOI：
10.1002/ijc.21120
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发表时间：
2005-10-20
影响因子：
6.4
通讯作者：
Inoue, H
中科院分区：
文献类型：
--
作者：
Kim, CJ;Yoshioka, N;Inoue, H
我们以前曾报道过，骨膜蛋白mRNA的表达在多种人类癌细胞系中显著降低，表明petiostin mRNA表达的下调与人类癌症的发展相关。本研究采用北方杂交和RT-PCR技术检测了人正常膀胱组织、膀胱癌组织和膀胱癌细胞系中periostin mRNA的表达，以探讨periostin在膀胱癌发生中的作用。在正常膀胱组织中有515例检测到periostin mRNA的表达，而在3株膀胱癌细胞系中未检测到periostin mRNA的表达。在1级、2级和3级膀胱癌组织中，骨膜蛋白mRNA的表达率分别为81.8%（9/11）、40.0%（4/10）和33.3%（4/12），表明骨膜蛋白mRNA的表达下调与膀胱癌的高级别密切相关（p < 0.05）。为了评估骨膜蛋白的肿瘤抑制功能，我们研究了骨膜蛋白基因抑制膀胱癌细胞系SBT 31 A恶性表型的能力。逆转录病毒载体异位表达petiostin基因抑制膀胱癌细胞的体外侵袭能力，而不影响细胞增殖和裸鼠肿瘤生长。骨膜蛋白还抑制小鼠黑色素瘤细胞系B16-F10的体内肺转移。突变分析显示，骨膜蛋白的C-末端区域足以抑制癌细胞的细胞侵袭和转移。Periostin可能在膀胱癌的侵袭和转移过程中起抑制作用。(c)2005 Wiley-Liss，Inc.
We have previously reported that expression of periostin mRNA is markedly reduced in a variety of human cancer cell lines, suggesting that downregulation of petiostin mRNA expression is correlated with the development of human cancers. In our study, to clarify the role of the periostin in human bladder carcinogenesis, we examined the expression of periostin mRNA in normal bladder tissues, bladder cancer tissues and bladder cancer cell lines by Northern blot analysis and RT-PCR analysis. Although the expression of periostin mRNA was detected in 100% (515) of normal bladder tissues, it was not detected in 3 human bladder cancer cell lines examined. It was also detected in 81.8% (9/11) of grade 1, 40.0% (4/10) of grade 2 and 33.3% (4/12) of grade 3 bladder cancer tissues, indicating that downregulation of periostin mRNA is significantly related to higher grade bladder cancer (p < 0.05). To assess the tumor suppressor function of periostin, we investigated the ability of periostin gene to suppress malignant phenotypes of a bladder cancer cell line, SBT31A. Ectopic expression of petiostin gene by a retrovirus vector suppressed in vitro cell invasiveness of the bladder cancer cells without affecting cell proliferation and tumor growth in nude mice. Periostin also suppressed in vivo lung metastasis of the mouse melanoma cell line, B16-F10. Mutational analysis revealed that the C-terminal region of periostin was sufficient to suppress cell invasiveness and metastasis of the cancer cells. Periostin may play a role as a suppressor of invasion and metastasis in the progression of human bladder cancers. (c) 2005 Wiley-Liss, Inc.