Kawanishi Hiroaki, Matsui Yoshiyuki, Ito Masaaki, Watanabe Jun, Takahashi Takeshi, Nishizawa Koji, Nishiyama Hiroyuki, Kamoto Toshiyuki, Mikami Yoshiki, Tanaka Yoshinori, Jung Giman, Akiyama Hideo, Nobumasa Hitoshi, Guilford Parry, Reeve Anthony, Okuno Yasushi, Tsujimoto Gozoh, Nakamura Eijiro, Ogawa Osamu
Department of Urology, Graduate School of Medicine, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Clin Cancer Res. 2008 May 1;14(9):2579-87. doi: 10.1158/1078-0432.CCR-07-1922.
The purpose of this study was to identify proteins that are potentially involved in the tumor invasion of bladder cancer.
We searched for the candidate proteins by comparing the profiles of secreted proteins among the poorly invasive human bladder carcinoma cell line RT112 and the highly invasive cell line T24. The proteins isolated from cell culture supernatants were identified by shotgun proteomics. We found that CXCL1 is related to the tumor invasion of bladder cancer cells. We also evaluated whether the amount of the chemokine CXCL1 in the urine would be a potential marker for predicting the existence of invasive bladder tumors.
Higher amount of CXCL1 was secreted from highly invasive bladder carcinoma cell lines and this chemokine modulated the invasive ability of those cells in vitro. It was revealed that CXCL1 regulated the expression of matrix metalloproteinase-13 in vitro and higher expression of CXCL1 was associated with higher pathologic stages in bladder cancer in vivo. We also showed that urinary CXCL1 levels were significantly higher in patients with invasive bladder cancer (pT1-4) than those with noninvasive pTa tumors (P = 0.0028) and normal control (P < 0.0001). Finally, it was shown that CXCL1 was an independent factor for predicting the bladder cancer with invasive phenotype.
Our results suggest that CXCL1 modulates the invasive abilities of bladder cancer cells and this chemokine may be a potential candidate of urinary biomarker for invasive bladder cancer and a possible therapeutic target for preventing tumor invasion.
本研究旨在鉴定可能参与膀胱癌肿瘤侵袭的蛋白质。
我们通过比较低侵袭性人膀胱癌细胞系RT112和高侵袭性细胞系T24之间的分泌蛋白谱来寻找候选蛋白质。从细胞培养上清液中分离出的蛋白质通过鸟枪法蛋白质组学进行鉴定。我们发现CXCL1与膀胱癌细胞的肿瘤侵袭有关。我们还评估了尿液中趋化因子CXCL1的量是否会成为预测侵袭性膀胱肿瘤存在的潜在标志物。
高侵袭性膀胱癌细胞系分泌的CXCL1量更高，并且这种趋化因子在体外调节了这些细胞的侵袭能力。结果显示，CXCL1在体外调节基质金属蛋白酶-13的表达，并且在体内CXCL1的高表达与膀胱癌的更高病理分期相关。我们还表明，侵袭性膀胱癌患者（pT1-4）的尿液CXCL1水平显著高于非侵袭性pTa肿瘤患者（P = 0.0028）和正常对照（P < 0.0001）。最后，结果表明CXCL1是预测具有侵袭性表型膀胱癌的独立因素。
我们的结果表明，CXCL1调节膀胱癌细胞的侵袭能力，并且这种趋化因子可能是侵袭性膀胱癌尿液生物标志物的潜在候选者以及预防肿瘤侵袭的可能治疗靶点。
