siRNA targeted against matrix metalloproteinase 11 inhibits the metastatic capability of murine hepatocarcinoma cell Hca-F to lymph nodes.
Matrix metalloproteinase-11 (MMP-11) belongs to the particular member of MMP family, a group of zinc-dependent endopeptidases involved in tumor progression, invasion and metastasis. MMP-11 is strongly expressed in tumor cells and stromal fibroblasts located in the immediate vicinity of tumor. This study investigated the possible role of MMP-11 expression in mouse hepatocarcinoma cell line Hca-F with highly lymphatic metastasis potential by RNA interference (RNAi) approach. The results showed that a small interfering RNA (siRNA) targeted against MMP-11 significantly impeded Hca-F cells proliferation and colony formation in soft agar, as well as resulted in Hca-F cell apoptosis. This reduction of MMP-11 expression also led to the decreased migration and adhesion of Hca-F cells dramatically both in vitro and in vivo. Furthermore, in vivo metastasis assay indicated that down-regulation of MMP-11 expression in Hca-F cells attenuated the metastatic potential of Hca-F cells to peripheral lymph nodes. These data together provide compelling evidence into the function of MMP-11 and suggest that MMP-11 act as a tumor lymphatic metastasis-associated gene, and could represent a new potential target for gene therapy.
Jia
Li
L
Department of Biochemistry, Institute of Glycobiology, College of Laboratory Medicine, Dalian Medical University, Liaoning Province, China.
Wang
Shujing
S
Cao
Jun
J
Zhou
Huimin
H
Wei
Wei
W
Zhang
Jianing
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology*; D053507:Matrix Metalloproteinase 11 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053507:Matrix Metalloproteinase 11