title: GHGKHKNK octapeptide (P-5m) inhibits metastasis of HCCLM3 cell lines via regulation of MMP-2 expression in in vitro and in vivo studies.
abstract: P-5m, an octapeptide derived from domain 5 of HKa, was initially found to inhibit the invasion and migration of melanoma cells. The high metastatic potential of melanoma cells was prevented by the HGK motif in the P-5m peptide in vitro and in an experimental lung metastasis model, suggesting that P-5m may play an important role in the regulation of tumor metastasis. The aim of this study was to measure the effect of P-5m on tumor metastasis of human hepatocarcinoma cell line (HCCLM3) in vitro and in vivo in a nude mouse model of hepatocellular carcinoma (HCC), and detect the mechanisms involved in P-5m-induced anti-metastasis. By gelatin zymography, matrix metallo-proteinases 2 (MMP-2) activity in HCCLM3 was dramatically diminished by P-5m peptide. In addition, the migration and metastasis of HCCLM3 cells was also inhibited by the peptide in vitro. In an orthotopic model of HCC in nude mice, P-5m treatment effectively reduced the lung metastasis as well as the expression of MMP-2 in the tumor tissues. Overall, these observations indicate an important role for P-5m peptide in HCC invasion and metastasis, at least partially through modulation MMP-2 expression. These data suggests that P-5m may have therapeutic potential in metastatic human hepatocarcinoma.
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China. hanxiaorumeng@126.com
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Yan
authors.forename: Xiang-Feng
authors.initials: XF
authors.lastname: Zhao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuura
authors.forename: Matsuura
authors.initials: M
authors.lastname: Hiroshi
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Ding
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Shuang
authors.initials: S
authors.lastname: Jiang
authors.forename: Bai-Rong
authors.initials: BR
authors.lastname: Du
authors.forename: Pei-Ge
authors.initials: PG
authors.lastname: Du
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D019679:Kininogen, High-Molecular-Weight / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009842:Oligopeptides / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; C419369:HKa protein, human; D019679:Kininogen, High-Molecular-Weight; D009842:Oligopeptides; D020778:Matrix Metalloproteinase 2