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Matrix Metalloproteinase-9 Silencing by RNA Interference Promotes the Adhesive-Invasive Switch in HT1080 Human Fibrosarcoma Cells by Zhu Xishan, Tai Weiping, Shi Wei, Song Yuguang, Zhang Hongmei, An Guangyu

Background: A high level of matrix metalloproteinase-9 (MMP-9) is associated with human tumor invasion and/or metastasis. The HT1080 human fibrosarcoma cell line is highly invasive and metastatic which constitutively express MMP-9.
Methods: HT1080 cells transfected with a double stranded RNA that targeted the MMP-9 mRNA and the cellular characteristics were examined before and after interference. The inhibition effects of MMP-9 interference on the tumor growth of HT1080 cells in nude mice was also tested by xenograft assay.
Results: MMP-9 extinction in HT1080 resulted in the following: (1) inhibited cell mobility; (2) increased cell ad-hesion, and (3) attenuated tumor cell migration. In addition, MMP-9 knockdown concomitantly resulted in decreased levels of soluble ICAM-1, leading to an adhesion defect and tumor metastasis. Moreover, in vivo assay further demonstrated MMP-9 interference affecting the tumorigenesis of HT1080 cells in mice as follows (1) inhi-bition of tumor growth; (2) reduced tumor volume, and (3) prolonged survival time.
Conclusions: Our observations defined a novel critical role for MMP-9 in the progression of HT1080 fibrosarcoma by changing the inter-cellular adhesion molecular-1 from membrane-anchored state to a soluble one which provides a target for promising tumor therapy in clinics.

DOI: Clin. Lab. 2012;58:313-322