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MMP-1/PAR-1通路在宫颈癌侵袭转移中的作用

Role of MMP-1/PAR-1 Signaling in the Cervical Cancer Invasion
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摘要 目的:探索基质金属蛋白酶-1(MMP-1)/蛋白酶活化受体-1(PAR-1)通路在宫颈癌侵袭转移中的作用。方法:RT-PCR法检测59例临床宫颈鳞癌组织和15例正常宫颈组织的MMP-1mRNA表达;Transwell实验检测添加重组人MMP-1及干扰PAR-1对宫颈癌Hela细胞转移侵袭能力的影响。结果:宫颈癌组织中的MMP-1(rhMMP-1)表达高于正常宫颈组织,并与侵袭转移程度相关;rhMMP-1能促进Hela细胞的转移能力,并与浓度相关;干扰PAR-1后能抑制MMP-1介导的Hela细胞转移能力。结论:MMP-1/PAR-1通路参与宫颈癌的侵袭转移,可能成为宫颈癌治疗的新靶点。 Objective: To investigate the role of matrix metalloproteinase-1 (MMP-1)/protease-activated receptors-1 (PAR-I) signaling in the cervical cancer invasion. Methods: RT-PCR was used to test the mRNA level of MMP-1 in 59 cases of cervical squamous cell cancer and 15 case of narmal cervical tissues. Transwell test was designed to explore the effect of adding recombinant human MMP-1 (rhMMP-1) and PAR-1-siRNA on cervical cancer (Hela cells) invasion. Results: In cervical cancer tissues more MMP-1 expression was observed than in normal cervical tissues, and its expression correlated with tumor status, rhMMP-1 could promote Hela cell invasion, and its number of invasive cell correlated with the concentration of rhMMP-1. Disrupting the expres- sion of PAR-1 reduced the MMP-1 promoting-effect on Hela cell invasion, but no effect on non-MMP-1 invasive action. Conclusion: The MMP-1/PAR-1 signaling is involved in cervical cancer invasion. Therefore, blocking PAR-1 may represent a new therapeutic option for metastatic cervical cancer.
出处 《生殖与避孕》 CAS CSCD 2014年第5期368-373,共6页 Reproduction and Contraception
基金 上海市卫生局课题资助项目 项目号:2011160
关键词 宫颈癌 基质金属蛋白酶-1(MMP-1) 蛋白酶活化受体-1(PAR-1) 侵袭 转移 cervical cancer matrix metalloproteinase- 1 (MMP- 1) protease-activated receptors- 1 (PAR- 1) metastasis invasion
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参考文献19

  • 1曹泽毅.中华妇产科学.2版.北京:人民卫生出版社,2006:2010-61.
  • 2王临虹,邱琇,郑睿敏,狄江丽.我国宫颈癌流行病学状况及防治策略的回顾与展望[J].中国妇幼卫生杂志,2010,1(3):146-149. 被引量:76
  • 3Hayashi K, Suzuki A, Ohno S, et al. PAR-1/MARK: a kinaseessential for maintaining the dynamic state of microtubules.Cell Struct Funct, 2012, 37(1):21-5.
  • 4Zigler M, Kamiya T, Brantley EC, et al. PAR-1 and thrombin:the ties that bind the microenvironment to melanomametastasis. Cancer Res, 2011, 71(21):6561-6.
  • 5Aronovich A, Nur Y, Shezen E, et al. A novel role for factorVIII and thrombin/ PAR1 in regulating hematopoiesis and itsinterplay with the bone structure. Blood, 2013, 122(15):2562-71.
  • 6金志军,徐晶,谢康云,张莺.宫颈癌组织中蛋白酶活化受体-1的表达与盆腔淋巴结转移的关系[J].生殖与避孕,2008,28(5):283-285. 被引量:2
  • 7Trivedi V, Boire A, Tchernychev B, et al. Platelet matrixmetalloprotease-1 mediates thrombogenesis by activatingPAR1 at a cryptic ligand site. Cell, 2009, 137(2):332-43.
  • 8Yang R, Xu Y, Li P, et al. Combined upregulation of matrixmetalloproteinase-1 and proteinase-activated receptor-1 predictsunfavorable prognosis in human nasopharyngealcarcinoma. Oncol Targets Ther, 2013, 6:1139-46.
  • 9Wang FQ, Fisher J, Fishman DA. MMP-1-PAR1 axis mediates LPA-induced epithelial ovarian cancer (EOC) invasion.Gynecol Oncol, 2011, 120(2):247-55.
  • 10Kaufmann R, Hollenberg MD. Proteinase-activated receptors (PARs) and calcium signaling in cancer. Adv Exp Med Biol,2012, 740:979-1000.

二级参考文献14

  • 1朱静鸿,孙丽琪,刘晓杰.长春市1987~2004年宫颈癌患者死亡分析[J].中国妇幼保健,2006,21(24):3387-3388. 被引量:3
  • 2Vu TKH,Huang DT,Wheaten VI,et al.Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation.Cell,1991,64 (6):1 057-68.
  • 3Baykal FLD,Horaist C,Yan CN,et al.Cloning and identification of regulatory sequences of the human thrombin receptor gene.J Biol Chem,1996,271(42):26 320-8.
  • 4Ossovskaya VS,Bunnett NW.Protease-activated receptors:contribution to physiology and disease.Physiol Rev,2004,84(2):579-621.
  • 5Junge CE,Lee C J,Hubbard KB,et al.Protease-activated receptor-l in human brain:localization and functional expression in astrocytes.Exp Neurol,2004,188(1):94-103.
  • 6Darmoul D,Gratio V,Devaud H,et al.Activation ofproteinase-activated receptor 1 promotes human colon cancer cell proliferation through epidermal growth factor receptor transactivation.Mol Cancer Res,2004,2(9):514-22.
  • 7Boire A,Covie L,Agarwal A,et al.PAR-Iis a matrixmetalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells.Cell,2005,120(3):303-13.
  • 8Liu Y,Gilcrease MZ,Henderson Y,et al Expression of protease-activated receptor 1 in oral squamous cell carcinoma.Cancer Lett,2001,169(2):173-80.
  • 9Liu J,Sehuff-Werner P,Steiner M.Double transfection improves small interfering RNA induced thrombin receptor (PAR-l)gene silencing in DU 145 prostate cancer cells.FEBS Lett,2004,577(1-2):175-80.
  • 10Grisaru-Granovsky S,Salah Z,Maoz M,et al.Differential expression of protease activated receptor 1(PAR-1)and pY397FAK in benign and malignant human ovarian tissue samples,lnt J Cancer,2005,113(3):372-8.

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