Notch配体Jagged2的高表达与膀胱尿路上皮癌的转移和复发相关。
High expression of Notch ligand Jagged2 is associated with the metastasis and recurrence in urothelial carcinoma of bladder.
作者信息
Li Wei, Liu Min, Feng Yuan, Huang Yan-Fei, Xu Yun-Fei, Che Jian-Ping, Wang Guang-Chun, Zheng Jun-Hua
机构信息
Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, 200072, China.
出版信息
Int J Clin Exp Pathol. 2013 Oct 15;6(11):2430-40. eCollection 2013.
BACKGROUND
The Notch signaling pathway is closely related with human organ development and tumorgenisis. Jagged2 is among the most popular topic in Notch studies currently. Recent studies found its vital role in tumor metastasis in breast cancer; however, its expression profile and its prognostic value in urothelial carcinoma of bladder have not been investigated.
METHODS
Immunohistochemistry was used to detect the expression of Jagged2 in 120 bladder urothelial carcinoma. Moreover, the expression of Jagged2 was analyzed by Western blot in 60 bladder urothelial carcinoma and 20 normal epithelial tissues. MTT assay and flow cytometry and transwell assay were used to examine the proliferative and invasive ability of bladder cancer cells with the treatment of GSIXX (the inhibitor of Jagged2). Prognostic value of Jagged2 expression and its correlation with tumor metastasis and recurrence were evaluated, and the proliferative and invasive ability and cell cycle process of the bladder cancer cells were detected as well.
RESULTS
There was a significantly higher Jagged2 expressions in bladder urothelial carcinoma and highly invasive bladder T24 cells than those in bladder normal tissues and the superficial bladder BIU-87 cells. Jagged2 expression was positively correlated with histological grade, p T stage, recurrence, and metastasis. With the increasing concentration of GSIXX, we found that not only the cell proliferation and invasion activity decreased significantly, but also the cell cycle was blocked at G2/M stage.
CONCLUSIONS
Jagged2 expression status was closely correlated with important histopathologic characteristics (grades and stages) and the recurrence and metastasis of bladder urothelial carcinomas. Furthermore, Jagged2 played an important function on the bladder cancer cells' proliferation by regulating the cancer cell cycle from G1/S to G2/M and probably promoted the invasion and metastasis of bladder cancer.
背景
Notch信号通路与人类器官发育和肿瘤发生密切相关。Jagged2是目前Notch研究中最热门的话题之一。最近的研究发现其在乳腺癌肿瘤转移中起重要作用；然而，其在膀胱尿路上皮癌中的表达谱及其预后价值尚未得到研究。
方法
采用免疫组织化学法检测120例膀胱尿路上皮癌中Jagged2的表达。此外，通过蛋白质免疫印迹法分析60例膀胱尿路上皮癌和20例正常上皮组织中Jagged2的表达。采用MTT法、流式细胞术和Transwell法检测经GSIXX（Jagged2抑制剂）处理的膀胱癌细胞的增殖和侵袭能力。评估Jagged2表达的预后价值及其与肿瘤转移和复发的相关性，并检测膀胱癌细胞的增殖、侵袭能力和细胞周期进程。
结果
膀胱尿路上皮癌和高侵袭性膀胱T24细胞中Jagged2的表达明显高于膀胱正常组织和浅表膀胱BIU-87细胞。Jagged2表达与组织学分级、pT分期、复发和转移呈正相关。随着GSIXX浓度的增加，我们发现不仅细胞增殖和侵袭活性显著降低，而且细胞周期阻滞在G2/M期。
结论
Jagged2表达状态与膀胱尿路上皮癌的重要组织病理学特征（分级和分期）以及复发和转移密切相关。此外，Jagged2通过调节癌细胞周期从G1/S到G2/M对膀胱癌细胞的增殖起重要作用，可能促进了膀胱癌的侵袭和转移。
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