切换至 "中华医学电子期刊资源库"

中华普通外科学文献(电子版) ›› 2009, Vol. 03 ›› Issue (04) : 280 -284. doi: 10.3877/cma.j.issn.1674-0793.2009.04.005

论著

CD44与乳腺癌化疗耐药的关系研究
姚和瑞1, 李志华2, 罗永辉2, 苏逢锡3,()   
  1. 1.510120 广州,中山大学附属第二医院肿瘤科
    2.南昌第三医院乳腺肿瘤中心
    3.510120 广州,中山大学附属第二医院乳腺肿瘤中心
  • 收稿日期:2008-08-26 出版日期:2009-08-01
  • 通信作者: 苏逢锡
  • 基金资助:
    国家自然科学基金资助课题(30671930)广东省医学科研基金资助课题(A2005226)广东省科技计划资助课题(2006B36002010)广东省自然科学基金资助课题(7001592)

Research of the relationship between CD44 and resistance of breast cancer chemotherapy

Herui YAO1, Zhi-hua LI1, Yong-hui LUO1, Feng-xi SU1,()   

  1. 1.Oncology Department of the Second Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China
  • Received:2008-08-26 Published:2009-08-01
  • Corresponding author: Feng-xi SU
引用本文:

姚和瑞, 李志华, 罗永辉, 苏逢锡. CD44与乳腺癌化疗耐药的关系研究[J]. 中华普通外科学文献(电子版), 2009, 03(04): 280-284.

Herui YAO, Zhi-hua LI, Yong-hui LUO, Feng-xi SU. Research of the relationship between CD44 and resistance of breast cancer chemotherapy[J]. Chinese Archives of General Surgery(Electronic Edition), 2009, 03(04): 280-284.

目的

CD44是细胞表面黏附分子,与乳腺癌的转移和预后关系密切,但其与乳腺癌化疗耐药的关系尚未明确。本研究主要探讨CD44与乳腺癌化疗耐药的关系。

方法

采用SP免疫组化的方法检测73例乳腺癌患者肿瘤组织CD44的表达,分析新辅助化疗敏感患者与耐药患者化疗前后CD44的表达情况;用RT-PCR和流式细胞免疫的方法检测乳腺癌细胞株MCF-7与其对应的阿霉素耐药细胞株MCF-7/ADR在mRNA和蛋白水平CD44的表达,并分析其差异。

结果

乳腺癌新辅助化疗耐药患者化疗前肿瘤组织CD44表达强于化疗敏感患者(χ2=4.22,P<0.05);耐药患者化疗后肿瘤组织CD44表达亦强于敏感患者(χ2=9.954,P<0.01);化疗前后比较发现化疗后肿瘤组织CD44表达较化疗前增高(t=3.43,P<0.01);耐药细胞株mRNA和蛋白水平CD44表达都升高。

结论

CD44表达与乳腺癌化疗耐药密切相关,可作为乳腺癌化疗耐药的预测指标,化疗可富集CD44阳性表达的肿瘤细胞。

Objective

CD44 is an adhesion molecule of cell surface, which is closely related with metastasis and prognosis of breast cancer,but the relationship between CD44 and drug resistance of breast cancer chemotherapy is not clear so far. We mainly study the relationship between CD44 and drug resistance of breast cancer chemotherapy.

Methods

The expression of CD44 was detected by SP immunohistochemical methods,the different expression of CD44 was investigated between drug-sensitive groups and drug-resistant groups of neoadjuvant chemotherapy,before and after chemotherapy.The different expressions of CD44 on the level of mRNA and protein in MCF-7 cell line and drug-resistant cell lines MCF-7/ADR was tested by reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry.

Results

Expression of CD44 before chemotherapy in drug-resistant groups was much higher than drug-sensitive ones(χ2=4.22,P <0.05). This was also found after chemotherapy(χ2=9.954,P<0.01).The expression of CD44 after chemotherapy was higher than that before chem otherapy (t=3.43,P<0.01).Expression of mRNA and protein of CD44 in MCF-7/ADR cell lines was higher than drug-sensitive cell lines (MCF-7).

Conclusion

CD44 may be conferred as a predictive index of breast cancer chemotherapy drug resistance,and chemotherapy may enrich CD44 positive breast cancer cell.

图1 CD44 免疫组化化疗后CD44 较化疗前表达增强,SD、PD 患者化疗后CD44 较CR、PR 患者表达更强
表1 非配对资料分析化疗前后肿瘤标本中CD44 的表达情况
图2 RT-PCR 检测两种细胞株CD44 表达差异耐药株MCF-7/ADR 的CD44 电泳条带明显强于敏感株MCF-7,定量分析结果亦提示MCF-7/ADR 的CD44 表达明显强于敏感株MCF-7
图3 流式细胞检测CD44,化疗耐药株比敏感株表达增高(P<0.01)
1
Watanabe O, Kinoshita J, Shimizu T, et al. Expression of a CD44 variant and VEGF-C and the implications for lymphatic metastasis and long-term prognosis of human breast cancer.J Exp Clin Cancer Res,2005,24(1):75-82.
2
贾海霞,苏逢锡,郭巨江,等.乳腺癌新辅助化疗的坐标法定位.中华普通外科杂志,2006,21(3):225.
3
许良中,杨文涛.免疫组织化学反应结果的判断标准.中国癌症杂志,1996,6(4):229-231.
4
Porter D,Lahti-Domenici J,Keshaviah A.Molecular markers in ductal carcinoma in situ of the breast.Mol Cancer Res,2003,1(5):362-375.
5
Matsumura Y,Train D.Significance of CD44 gene products for cancer diagnosis and disease evalution.Lancet,1992,340(8827):1053-1058.
6
Kaufmann M, Heider KH, Sinn HP, et al. CD44 variant exon epitopes in primary breast cancer and length of survival. Lancet, 1995, 345(89 50):615-619.
7
Tokue Y,Matsumura Y,Katsumata N,et al.CD44 variant isoform expression and bresat cancer prognosis.Jpn J Cancer Res,1998,89(3):283-290.
8
Yu Q,Toole BP,Stamenkovic I.Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function.J Exp Med,1997,186(12):1985-1996.
9
De la Torre M, Heldin P, Bergh J. Expression of the CD44 glycoprotein(1ymphocyte-homing receptor)in untreated human breast cancer and its relationship to prognostic markers.Anticancer Res,1995,15(6B):2791-2795.
10
Al-Hajj M,Wicha MS,Benito-Hernandez A,et al.Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci USA,2003,100(7):3983-3988.
11
Pu RT,Schott AF,Sturtz DE,et al.Pathologic features of breast cancer associated with complete response to neoadjuvant chemotherapy: importance of tumor necrosis.Am J Surg Pathol,2005,29(3):354-358.
12
Gerson SL.Drug resistance gene transfer:Stem cell protection and therapeutic efficacy.Exp Hematol,2000,28(12):1315-1324.
13
Dean M,Fojo T,Bates S.Tumour stem cells and drug resistance.Nat Rev Cancer,2005,5(4):275-284.
14
Donnenberg VS,Donnenberg AD.Multiple drug resistance in cancer revisited:thecancerstemcellhypothesis.JClinPharmacol,2005,45(8):872-877.
[1] 洪玮, 叶细容, 刘枝红, 杨银凤, 吕志红. 超声影像组学联合临床病理特征预测乳腺癌新辅助化疗完全病理缓解的价值[J]. 中华医学超声杂志(电子版), 2024, 21(06): 571-579.
[2] 杨柳, 宋振川, 王新乐. 乳腺癌改良根治术联合背阔肌复位的临床疗效评估[J]. 中华乳腺病杂志(电子版), 2024, 18(05): 269-273.
[3] 王聪, 李云涛, 唐甜甜, 王鑫蕊, 吕鑫, 范志刚. 多基因检测对激素受体阳性、HER-2阴性乳腺癌新辅助化疗疗效预测的研究进展[J]. 中华乳腺病杂志(电子版), 2024, 18(05): 292-296.
[4] 许杰, 李亚俊, 冯义文. SOX新辅助化疗后腹腔镜胃癌D2根治术与常规根治术治疗进展期胃癌的近期随访比较[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 647-650.
[5] 张钊, 骆成玉, 张树琦, 何平, 李旭斌. 不同术式治疗早期乳腺癌的效果及并发症发生率、复发率比较[J]. 中华普外科手术学杂志(电子版), 2024, 18(05): 494-497.
[6] 宋佳, 汪波, 孙凯律, 商江峰, 吴旦平, 肇毅. 吲哚菁绿荧光显影联合亚甲蓝染色在乳腺癌前哨淋巴结活检中的应用[J]. 中华普外科手术学杂志(电子版), 2024, 18(05): 498-501.
[7] 孙建娜, 孔令军, 任崇禧, 穆坤, 王晓蕊. 266例首诊Ⅳ期乳腺癌手术患者预后分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(05): 502-505.
[8] 唐丹萍, 王萍, 江孟蝶, 杨晓蓉. 自体脂肪移植在乳腺癌术后乳房重建的研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(05): 582-585.
[9] 张昊, 潘卫东. 胰腺癌新辅助化疗后可切除性评估现状及进展[J]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 629-633.
[10] 王军华, 王锐炫. 胰腺癌新辅助化疗现状和治疗策略[J]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 640-643.
[11] 王向前, 李清峰, 陈磊, 丘文丹, 姚志成, 李熠, 吴荣焕. 姜黄素抑制肝细胞癌索拉非尼耐药作用及其调控机制[J]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 729-735.
[12] 王帅, 张志远, 苏雨晴, 李雯雯, 王守凯, 刘琦, 李文涛. 孟德尔随机化及其在乳腺癌研究中的应用进展[J]. 中华临床医师杂志(电子版), 2024, 18(07): 671-676.
[13] 崔军威, 蔡华丽, 胡艺冰, 胡慧. 亚甲蓝联合金属定位夹及定位钩针标记在乳腺癌辅助化疗后评估腋窝转移淋巴结的临床应用价值探究[J]. 中华临床医师杂志(电子版), 2024, 18(07): 625-632.
[14] 王誉英, 刘世伟, 王睿, 曾娅玲, 涂禧慧, 张蒲蓉. 老年乳腺癌新辅助治疗病理完全缓解的预测因素分析[J]. 中华临床医师杂志(电子版), 2024, 18(07): 641-646.
[15] 徐靖亭, 孔璐. PARP抑制剂治疗卵巢癌的耐药机制及应对策略[J]. 中华临床医师杂志(电子版), 2024, 18(06): 584-588.
阅读次数
全文


摘要