DDR1在唾液腺黏液表皮样癌中的表达及意义

上海口腔医学 ›› 2016, Vol. 25 ›› Issue (3): 322-326.

DDR1在唾液腺黏液表皮样癌中的表达及意义

王智明¹, 温惠媛¹, 杨东升¹, 叶明¹, 潘遥¹, 马颖², 张力平¹

1.中国医科大学附属盛京医院口腔颌面外科;
2. 病理科,辽宁沈阳 110004

收稿日期:2016-01-06 修回日期:2016-03-08 出版日期:2016-06-25 发布日期:2016-07-22
通讯作者: 王智明,E-mail: wangzm@sj-hospital.org
作者简介:王智明（1972-）,男,博士,副教授,硕士研究生导师
基金资助:
辽宁省科学技术计划项目资助（2012225100）

Expression and significance of discoidin domain receptor 1 in salivary gland mucoepidermoid carcinoma

WANG Zhi-ming¹, WEN Hui-yuan¹, YANG Dong-sheng¹, YE Ming¹, PAN Yao¹, MA Ying², ZHANG Li-ping¹

1.Department of Oral and Maxillofacial Surgery;
2. Department of Pathology, Shengjing Hospital of China Medical University. Shenyang 110004, Liaoning Province, China

Received:2016-01-06 Revised:2016-03-08 Online:2016-06-25 Published:2016-07-22

摘要/Abstract

摘要： 目的探讨盘状结构域受体1（discoidin domain receptor 1,DDR1）在唾液腺黏液表皮样癌（mucoepidermoid carcinoma,MEC）中的表达及意义。方法采用免疫组织化学和Western 免疫印迹技术检测MEC细胞株M3SP2和MC3中DDR1的表达情况。应用免疫组织化学方法检测58例唾液腺MEC组织及20例正常唾液腺组织中DDR1的表达,采用SPSS13.0 软件包对数据进行统计学分析。结果 DDR1在黏液表皮样癌组织中的阳性表达率为79.3%,显著高于正常唾液腺组织（10%,P<0.01）。DDR1的高表达与MEC的临床病理参数无显著相关性（P>0.05）。在黏液表皮癌细胞株M3SP2和MC3中,DDR1表达阳性。结论 DDR1在唾液腺MEC的发生、发展中可能发挥重要作用。

关键词: 盘状结构域受体1, 唾液腺, 黏液表皮样癌

Abstract: PURPOSE: To investigate the expression and significance of discoidin domain receptor 1 (DDR1) in salivary gland mucoepidermoid carcinoma (MEC). METHODS: Immunohistochemical and Western blot method were used to detect the expression of DDR1 in MEC M3SP2 and MC3 cell lines. Immunohistochemical method was used to detect the expression of DDR1 in 58 MEC and 20 normal salivary gland tissues. SPSS 13.0 software package was used for statistical analysis. RESULTS: The positive expression rate of DDR1 in salivary gland MEC tissues was 79.3%, significantly higher than 10.0% in normal salivary gland tissues (P<0.01). High expression of DDR1 was not related to clinicopathological parameters of MEC(P>0.05). The expression of DDR1 was positive in MEC M3SP2 and MC3 cell lines. CONCLUSIONS: DDR1 may play an important role in carcinogenesis and progress of salivary gland MEC.

Key words: Discoidin domain receptor 1, Salivary gland, Mucoepidermoid carcinoma

中图分类号:

R739.8

王智明, 温惠媛, 杨东升, 叶明, 潘遥, 马颖, 张力平. DDR1在唾液腺黏液表皮样癌中的表达及意义[J]. 上海口腔医学, 2016, 25(3): 322-326.

WANG Zhi-ming, WEN Hui-yuan, YANG Dong-sheng, YE Ming, PAN Yao, MA Ying, ZHANG Li-ping. Expression and significance of discoidin domain receptor 1 in salivary gland mucoepidermoid carcinoma[J]. Shanghai Journal of Stomatology, 2016, 25(3): 322-326.

参考文献

[1] 于世凤. 口腔组织病理学 [M]. 第6版. 北京: 人民卫生出版社, 2007: 287-288.
[2] 温玉明, 代晓明, 王昌美, 等. 口腔颌面部恶性肿瘤6539例临床病理分析 [J]. 华西口腔医学杂志, 2001, 19(5): 296-299.
[3] Grassot J, Gouy M, Perrière G, et al. Origin and molecular evolution of receptor tyrosine kinases with immunoglobulin-like domains [J]. Mol Biol Evol, 2006, 23(6): 1232-1241.
[4] Luo LY, Hahn WC. Oncogenic signaling adaptor proteins [J]. J Genet Genomics, 2015, 42(10): 521-529.
[5] 蒋毅, 马静, 韩代书. Tyro3受体酪氨酸激酶亚家族的研究进展 [J]. 中国组织化学与细胞化学杂志, 2005, 14(4): 466-469.
[6] Di Marco E, Cutuli N, Guerra L, et al. Molecular cloning of trkE, a novel trk-related putative tyrosine kinase receptor isolated from normal human keratinocytes and widely expressed by normal human tissues [J]. J Biol Chem, 1993, 268(32): 24290-24295.
[7] Alves F, Vogel W, Mossie K, at al. Distinct structural characteristics of discoidin I subfamily receptor tyrosine kinases and complementary expression in human cancer [J]. Oncogene, 1995, 10(3): 609-618.
[8] Malaguarnera R, Nicolosi ML, Sacco A, et al. Novel cross talk between IGF-IR and DDR1 regulates IGF-IR trafficking, signaling and biological responses [J]. Oncotarget, 2015, 6(18): 16084-16105.
[9] Faraci E, Eck M, Gerstmayer B, et al. An extracellular matrix-specific microarray allowed the identification of target genes downstream of discoidin domain receptors [J]. Matrix Biol, 2003, 22(4): 373-381.
[10] Carbone A, Gloghini A. Activated DDR1 increases RS cell survival [J]. Blood, 2013, 122(26): 4152-4154.
[11] Reel B, Korkmaz CG, Arun MZ, et al. The regulation of matrix metalloproteinase expression and the role of discoidin domain receptor 1/2 signalling in zoledronate-treated PC3 cells [J]. J Cancer, 2015, 6(10): 1020-1029.
[12] Dejmek J, Leandersson K, Manjer J, et al. Expression and signaling activity of Wnt-5a/discoidin domain receptor-1 and Syk plays distinct but decisive roles in breast cancer patient survival [J]. Clin Cancer Res, 2005, 11(2 Pt 1): 520-528.
[13] Ongusaha PP, Kim JI, Fang L, et al. p53 induction and activation of DDR1 kinase counteract p53-mediated apoptosis and influence p53 regulation through a positive feedback loop [J]. EMBO J, 2003, 22(6): 1289-1301.
[14] Quan J, Yahata T, Adachi S, et al. Identification of receptor tyrosine kinase, discoidin domain receptor 1 (DDR1), as a potential biomarker for serous ovarian cancer [J]. Int J Mol Sci, 2011, 12(2): 971-982.
[15] Shimada K, Nakamura M, Ishida E, et a1. Prostate cancer antigen-1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer [J]. Cancer Sci, 2008, 99(1): 39-45.
[16] 黄海涛, 刘华蔚, 王如, 等. 412例腮腺恶性肿瘤回顾分析 [J]. 上海口腔医学, 2014, 23(3): 340-345.
[17] 周全, 刘洪刚, 金玉兰, 等. 颈部淋巴结黏液表皮样癌 [J]. 临床与实验病理学杂志, 2009, 25(1): 41-45.
[18] 吴红珍, 江新青, 魏新华, 等. 腮腺黏液表皮样癌的CT诊断及鉴别诊断(附3例报告) [J]. 中国CT和MRI杂志, 2015, 13(2): 10-11.
[19] 张惠, 向素芳, 邓立强, 等. 涎腺黏液表皮样癌的超声表现及病理学基础 [J]. 四川医学, 2014, 35(9): 1235-1236.
[20] 史璐, 陈新明, 陈智, 等. 小涎腺黏液表皮样癌临床病理及血管生成的研究 [J]. 口腔医学研究, 2010, 26(4): 524-528.
[21] 赵尔杨, 王姗, 施磊, 等. 口腔黏膜癌中HIF-1a、VEGF表达与血管生成关系的研究 [J]. 口腔医学研究, 2009, 25(5): 545-547.
[22] Johnson JD, Edman JC, Rutter WJ. A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain [J]. Proc Natl Acad Sci USA, 1993, 90(12):5677-5681.
[23] Ferri N, Carragher NO, Raines EW. Role of discoidin domain receptors 1 and 2 in human smooth muscle cell-mediated collagen remodeling: potential implications in atherosclerosis and lymphangioleiomyomatosis [J]. Am J Pathol, 2004, 164(5): 1575-1585.
[24] Shyu KG, Chao YM, Wang BW, et al. Regulation of discoidin domain receptor 2 by cyclic mechanical stretch in cultured rat vascular smooth muscle cells [J]. Hypertension, 2005, 46(3): 614-621.
[25] Lee R, Eidman KE, Kren SM, et al. Localization of discoidin domain receptors in rat kidney [J]. Nephron Exp Nephrol, 2004, 97(2): e62-70.
[26] Matsuyama W, Watanabe M, Shirahama Y, et al. Activation of discoidin domain receptor 1 on CD14-positive bronchoalveolar lavage fluid cells induces chemokine production in idiopathic pulmonary fibrosis [J]. J Immunol, 2005, 174(10): 6490-6498.
[27] Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, et al. Overexpression of the cell adhesion molecules DDR1, Claudin 3, and Ep-CAM in metaplastic ovarian epithelium and ovarian cancer [J]. Clin Cancer Res, 2014, 10(13): 4427-4436.
[28] Ford CE, Lau SK, Zhu CQ, et al. Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma [J]. Br J Cancer, 2007, 96(5): 808-814.
[29] Yang J, Liu J, Zhong M, et al. Discoidin domain receptors: a promoter of the aggressive behavior of ameloblastomas [J]. IUBMB Life, 2014, 66(4): 292-299.
[30] 李超, 向小勇, 陈力, 等. 盘状结构域受体1在食管鳞癌组织中的表达 [J]. 重庆医科大学报, 2008, 33(9): 1115-1117.
[31] Neuhaus B, Bühren S, Böck B, et al. Migration inhibition of mammary epithelial cells by Syk is blocked in the presence of DDR1 receptors [J]. Cell Mol Life Sci, 2011, 68(22): 3757-3770.
[32] Miao L, Zhu S, Wang Y, et a1. Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung cancer and promotes cell invasion via epithelial-to-mesenchymal transition [J]. Med Oncol, 2013, 30(3): 626-634.
[33] Valencia K, Ormazábal C, Zandueta C, et al. Inhibition of collagen receptor discoidin domain receptor-1(DDR1) reduces cell survival, homing, and colonization in lung cancer bone metastasis [J]. Clin Cancer Res, 2012, 18(4):969-980.