The C-terminal flanking peptide of progastrin induces gastric cell apoptosis and stimulates colonic cell division in vivo

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2013-08, Vol.46, p.83-93
• Main Authors: Marshall, Kathryn M., Patel, Oneel, Bramante, Gianni, Laval, Marie, Yim, Mildred, Baldwin, Graham S., Shulkes, Arthur
• Format: Article
• Language: English
• Subjects: animal models; Animals; Apoptosis; bioactive properties; C-terminal flanking peptide; Cancer; cell division; Cell Division - physiology; Cell Line, Tumor; Cell Movement; Cell Proliferation; colon; CRC; Female; gastric mucosa; Gastric Mucosa - metabolism; gastrins; Gastrins - deficiency; Gastrins - genetics; Gastrins - metabolism; Ggly; Heterografts; Humans; liver; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Male; males; metastasis; Mice; Mice, Inbred CBA; Mice, Knockout; Mice, SCID; Mouse; Neoplasm Invasiveness; Neoplasm Transplantation; neoplasms; Peptide Fragments - metabolism; Progastrin; Protein Precursors - metabolism; severe combined immunodeficiency
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2013.05.009

•The C-terminal flanking peptide (CTFP) of progastrin is bioactive in vitro.•CTFP increases colon proliferation in vivo.•CTFP is pro-apoptotic in male mouse stomachs.•CTFP did not enhance xenograft or metastatic tumor growth in vivo. Progastrin (PG) is processed into a number of smaller peptides including amidated gastrin (Gamide), non-amidated glycine-extended gastrin (Ggly) and the C-terminal flanking peptide (CTFP). Several groups have reported that PG, Gamide and Ggly are biologically active in vitro and in vivo, and are involved in the development of gastrointestinal cancers. CTFP is bioactive in vitro but little is known of its effects in vivo. This study investigated the bioactivity of CTFP in vivo in normal tissues using gastrin deficient (GASKO) mice and in two mouse models of cancer (SCID mice bearing xenograft tumors expressing normal or knocked-down levels of gastrin and a mouse model of hepatic metastasis). As with Ggly, CTFP treatment stimulated colonic proliferation in GASKO mice compared to control. CTFP also significantly increased apoptosis in the gastric mucosa of male GASKO mice. CTFP did not appear to effect xenograft growth or the incidence of liver metastases. This is the first demonstration that CTFP has specific biological activity in vivo in the colon and stomach.