膀胱移行细胞癌中粘蛋白MUC1的表达与肿瘤浸润性树突状细胞的分布

南方医科大学学报 ›› 2005, Vol. 25 ›› Issue (09): 1114-1118.

膀胱移行细胞癌中粘蛋白MUC1的表达与肿瘤浸润性树突状细胞的分布

向松涛¹, 周四维², 管维², 刘继红², 叶章群²

1. 广州中医药大学附属省中医院泌尿外科, 广东, 广州, 510120;
2. 华中科技大学同济医学院泌尿外科, 湖北, 武汉, 430030

出版日期:2005-09-20 发布日期:2005-09-20
基金资助:
收稿日期:2005-3-4。
基金项目:国家自然科学基金(30271300)
作者简介:向松涛(1969- ),男,2003年毕业于华中科技大学同济医学院,博士,主治医师,E-mail:tonyxst@163.com
通讯作者:周四维,教授,博士导师,电话:027-83662364.

Expression of MUC1 and distribution of tumor-infiltrating dentritic cells in human bladder transitional cell carcinoma

XIANG Song-tao¹, ZHOU Si-wei², GUAN Wei², LIU Ji-hong², YE Zhang-qun²

1. 广州中医药大学附属省中医院泌尿外科, 广东, 广州, 510120;
2. 华中科技大学同济医学院泌尿外科, 湖北, 武汉, 430030

Online:2005-09-20 Published:2005-09-20

摘要/Abstract

摘要： 目的研究膀胱移行细胞癌中粘蛋白MUC1表达和肿瘤浸润性树突状细胞(TIDC)分布的变化,探讨二者在膀胱癌侵袭、转移及化疗耐药过程中的作用。方法采用免疫组织化学SP法检测MUC1和TIDC在膀胱移行细胞癌的表达和定位及MUC1在T-24细胞、BIU-87和耐药株BIU-87/A中的表达。应用流式细胞仪检测BIU-87、耐药株BIU-87/A及T-24细胞在阿霉素、长春新碱、顺铂3种化疗药物作用48h后的凋亡率。结果 MUC1在各期膀胱移行细胞癌中均表达,表达模式各有特点,MUC1的染色分型同肿瘤的病理分级和临床分期密切相关(P<0.001)。DC的数量同肿瘤病理分级呈负相关,随着病理分级的升高阳性细胞数明显减少(P<0.005)。MUC1在BIU-87、T-24细胞膜、胞浆中均有浅棕色弱阳性表达,在BIU-87/A的胞膜、胞浆中均有深棕色强阳性表达,两者细胞平均光密度值差异有显著性(P<0.01)。流式细胞仪检测BIU-87、T-24和BIU-87/A的自发凋亡率分别为1.15%、1.40%、0.90%,在阿霉素、长春新碱、顺铂3种化疗药物作用48h后,BIU-87的凋亡率分别为45.69%、47.70%、44.50%,T-24的凋亡率分别为43.79%、46.17%、44.50%,均有明显升高(P<0.01),但两种细胞之间及3种化疗药之间差异无显著性(P>0.05)。耐药株BIU-87/A在阿霉素、长春新碱作用48h后的凋亡率分别为19.88%、21.41%,均明显低于亲本细胞株BIU-87(P<0.05)。结论 MUC1的表达模式和TIDC数量的监测可以作为膀胱移行细胞癌恶性程度和预后的判断指标。TIDC的减少可能是膀胱癌免疫逃逸和耐受的重要环节,肿瘤细胞表面高密度的MUC1可能参与膀胱移行细胞癌侵袭转移和化疗耐药机制。

Abstract: Objective To study MUC1 expression and distribution of tumor-infiltrating dentritic cells (TIDCs) in human bladder transitional cell carcinoma (BTCC). Methods Immunohistochemical staining was employed to detect MUC1 expression and TIDC distribution in 69 surgical specimens of BTCC. MUC1 expression was also detected immunohistochemically in BIU-87, T-24 and drug-resistant BIU87/A cells. Flow cytometry was performed for determining the apoptosis rates of these 3 cells after a 48-hour treatment with adriamycin, vincristine and cisplatin, respectively. Results MUC1 expression was detected in the BTCC tissues of all stages and the immunohistochemical staining patterns were significantly associated with the pathological grade and clinical stage of the tumors (P<0.001). The number of TIDCs in the tumors was inversely correlated with tumor pathological grades and clinical stages (P<0.005). MUC1 expressed weakly in the cytoplasm and on the membrane of BIU-87 cells and T-24 cells, but strongly in the cytoplasm and membrane of BIU-87/A cells, showing significant differences between the drug-sensitive and-resistant cells (P<0.05). The apoptosis rates of BIU-87 cells and T-24 cells increased obviously after treatment with adriamycin, vincristine and cisplatin, but no significant differences were noted between the two cells or between the 3 drugs. The apoptosis rate of BIU87/A cells, however, exhibited no obvious increase after adriamycin or vincristine treatment, but showed significant increase in response to cisplatin treatment (P<0.05). Conclusions The expression pattern of MUC1 and distribution of TIDCs can be useful markers to evaluate the degree of malignancy and prognosis of BTCC. The decrease in the number of TIDCs may have important relation to tumor immune evasion and immune tolerance, and MUC1 over-expression may lead to drug resistance of BTCC, indicating its involvement in tumor infiltration and metastasis.

中图分类号:

R737.14

向松涛¹, 周四维², 管维², 刘继红², 叶章群². 膀胱移行细胞癌中粘蛋白MUC1的表达与肿瘤浸润性树突状细胞的分布[J]. 南方医科大学学报, 2005, 25(09): 1114-1118.

XIANG Song-tao¹, ZHOU Si-wei², GUAN Wei², LIU Ji-hong², YE Zhang-qun². Expression of MUC1 and distribution of tumor-infiltrating dentritic cells in human bladder transitional cell carcinoma[J]. Journal of Southern Medical University, 2005, 25(09): 1114-1118.

参考文献

[1] Lesuffleur T, Zweibaum A, Real FX. Mucins in normal and neoplastic human gastrointestinal tissues [J]. Crit Rev Oncel Hematol, 1994,17(3):153-80.
[2] Hanski C, Hofmeier M, Schmitt-Graff A, et al. Overexpression or ectopic expression of MUC2 is the common property of mucinous carcinomas of the colon, pancreas, breast and ovary [J].J Pathol,1997, 182(4):385-91.
[3] Chen Y, Wang Y, Xu W, et al. Analysis on the mechanism of Helicobacter pylori-induced apoptosis in gastric cancer cell line BGC-823 [J]. Int J Mol Med, 2005, 16(4):741-45.
[4] Troy AJ, Summers KL, Davidson PJT, et al. Minimal recruitment and activation of dendritic cells within renal cell carcinoma[J]. Clin Cancer Res, 1998, 4(3):585-93.
[5] Tsujitani S, Kakeji Y, Watanabe A, et al. Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer[J]. Cancer, 1990, 66(9):2012-6.
[6] Kim YS, Gum J Jr, Brockhausen I. Mucin glycoproteins in neoplasia [J]. Glycoconj J, 1996,13(5):693-707.
[7] Seregni E, Botti C, Massaron S, et al. Structure, function and gene expression of epithelial mucins[J]. Tumori, 1997, 83 (3):625-32.
[8] Roussel P, Lamblin G, Lhermitte M, et al. The complexity of mucins[J]. Biochimie, 1988, 70(4):1471-82.
[9] Packer LM, Williams SJ, Callaghan S, et al. Expression of the cell surface mucin gene family in adenocarcinomas [J]. Int Oncol, 2004,25(4):1119-26.
[10] Lau SK, Weiss LM, Chu PG. Differential expression of MUC 1, MUC2,and MUC5AC in carcinomas of various sites:an immunohistochemical study[J]. Am J Clin Pathol, 2004,122(1):61-9.
[11] Nassar H, Pansare V, Zhang H, et al. Pathogenesis of invasive micropapillary carcinoma:role of MUC 1 glycoprotein [J]. Mod Pathol,2004,17(9):1045-50.
[12] Kunze E, Francksen B, Schulz H, et al. Expression of MUC5AC apomucin in transitional cell carcinomas of the urinary bladder and its possible role in the development of mucus-secreting adenocarcinomas[J]. Virchows Arch, 2001, 439(5):609-15.