title: Hepatocyte growth factor ameliorates mucosal injuries leading to inhibition of colon cancer development in mice.
abstract: Hepatocyte growth factor (HGF), which facilitates the repair of injured mucosa, has the potential to be a new therapeutic agent for inflammatory bowel disease (IBD). However, given that the incidence of colorectal cancer increases continuously with disease duration in patients with IBD, the fact that HGF is a potent mitogen for intestinal epithelial cells may further heighten the risk of bowel cancer in this patient population. In this study, we examined the effects of recombinant HGF on colorectal cancer development in mice with or without experimentally induced colitis. Although HGF stimulated proliferation of colonic epithelial cells in normal mucosa, the development of colorectal cancer induced by repeated injection of azoxymethane (AOM) was significantly inhibited by HGF treatment. In a mouse model of colitis-associated cancer, colorectal cancer frequently developed despite only a single injection of AOM prior to three cycles of dextran sulfate sodium administration. However, HGF treatment significantly facilitated the repair of injured mucosa, leading to inhibition of colorectal cancer development in a dose-dependent manner. Thus, HGF-induced repair of injured mucosa inhibits rather than accelerates the development of colorectal cancer, and these results also suggest the importance of blocking the cycles of mucosal injury and repair to prevent colitis-associated colorectal cancer.
authors.affiliation: HGF Hepatic Regeneration Therapy Project, Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Yamaji
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Akihiro
authors.initials: A
authors.lastname: Moriuchi
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Numata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Setoyama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tamai
authors.forename: Keita
authors.initials: K
authors.lastname: Funakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Toshio
authors.initials: T
authors.lastname: Sakiyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uto
authors.forename: Makoto
authors.initials: M
authors.lastname: Oketani
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor