Secreted CXCL1 is a potential mediator and marker of the tumor invasion of bladder cancer
Secreted CXCL1 is a potential mediator and marker of the tumor invasion of bladder cancer
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DOI：
10.1158/1078-0432.ccr-07-1922
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发表时间：
2008-05-01
影响因子：
11.5
通讯作者：
Ogawa, Osamu
中科院分区：
文献类型：
--
作者：
Kawanishi, Hiroaki;Matsui, Yoshiyuki;Ogawa, Osamu
目的：本研究的目的是确定可能参与膀胱癌肿瘤侵袭的蛋白质。实验设计：我们通过比较低侵袭性人膀胱癌细胞系RT 112和高侵袭性细胞系T24之间的分泌蛋白质谱来寻找候选蛋白质。通过鸟枪蛋白质组学鉴定从细胞培养上清液中分离的蛋白质。我们发现CXCL 1与膀胱癌细胞的肿瘤侵袭有关。我们还评估了尿中趋化因子CXCL 1的量是否是预测浸润性膀胱肿瘤存在的潜在标志物。结果：高浸润性膀胱癌细胞系分泌较高量的CXCL 1，这种趋化因子调节这些细胞的体外侵袭能力。CXCL 1在体外可调节基质金属蛋白酶13的表达，在体内膀胱癌中CXCL 1的高表达与较高的病理分期相关。浸润性膀胱癌（pT 1 -4）患者尿CXCL 1水平显著高于非浸润性pTa肿瘤（P = 0.0028）和正常对照（P < 0.0001）。结论：CXCL 1可调节膀胱癌细胞的侵袭能力，CXCL 1有可能成为膀胱癌侵袭性生物标志物的候选者，并可能成为膀胱癌侵袭性的治疗靶点。
Purpose: The purpose of this study was to identify proteins that are potentially involved in the tumor invasion of bladder cancer.Experimental Design: 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.Results: 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.Conclusions: 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.