Membrane type I-matrix metalloproteinase promotes human prostate cancer invasion and metastasis

作者：Cao J^*; Chiarelli C; Kozarekar P; Adler HL

来源：Thrombosis and Haemostasis, 2005, 93(4): 770-778.

DOI：10.1160/TH04-08-0555

• MTI-MMP
• cell migration
• invasion
• metastasis
• prostate cancer

Development of metastases requires cancer cells to breach underlying basement membrane, migrate through interstitial stroma and gain access to blood or lymphatic vessels. Membrane type I-matrix metalloproteinase (MTI-MMP) has been linked with these processes. Expression of MTI-MMP in human prostate cancer correlates with the stage of this disseminated disease. The mechanism underlying this observation, however, still remains to be understood. To study the role of MTI-MMP in prostate cancer dissemination, endogenous and recombinant MTI-MMP expressed in human prostate cancer cell lines (DU-145 and LNCaP) were examined. Using FITC-labeled Matrigel, a soluble basement membrane extract coated coverslips, LNCaP cells stably expressing a chimera of MTI-MMP and Green Fluorescent Protein (MTI-GFP) degraded Matrigel and readily migrated over degraded substrates. The degradation of Matrigel by LNCaP cells expressing MTI-GFP was sensitive to MMP inhibitors, CT-1746 and TIMP-2, but notTIMP-1. Cell migration was dramatically enhanced by expression of MTI-MMR By employing surgical orthotopic implantation of LNCaP cells stably expressing MTI-GFP into the prostate gland of immunodeficient mice, we demonstrated that MTl-MMP promotes lymph node and lung metastasis of prostate cancer cells. Together, these results emphasize the pivotal role of MTI-MMP in prostate cancer dissemination and confirm that MTI-MMP is a suitable target to prevent cancer metastasis.

• 出版日期2005-4