title: Gastric epithelial cells secrete a PDGF-like peptide, a potent mitogen for human gastric fibroblasts.
abstract: To investigate whether gastric epithelial cells secrete growth factors involved in stromal cell growth, we examined the effects of conditioned media obtained from gastric cancer cells on murine BALB/c 3T3 cells and primary cultured human gastric fibroblasts. Conditioned media from MKN-1 gastric cancer cells were applied to a heparin-affinity column. The fraction eluted from the column at 0.4 M NaCl stimulated DNA synthesis and phosphorylation of PDGF alpha-receptors on tyrosine in BALB/c 3T3 cells. The fraction-induced stimulation of DNA synthesis in gastric fibroblasts was more marked than in BALB/c 3T3 cells. However, the fraction failed to stimulate DNA synthesis in CHO-ER cells overexpressing EGF receptors and phosphorylation of PDGF beta-receptors on tyrosine in BALB/c 3T3 cells. Immunoblot analysis of the media confirmed that PDGF-AA-like peptides are released from gastric cancer cells, immortalized gastric epithelial cells, and primary cultured gastric epithelial cells. Anti-PDGF neutralizing antibodies produced only a partial inhibition of 0.4 M NaCl fraction-induced enhanced DNA synthesis. Thus, in addition to PDGF-AA peptide, other bioactive substance(s) are probably released from MKN-1 gastric cancer cells. Our results suggest that gastric epithelial cells secrete PDGF-AA-like peptides responsible for stromal cell growth through paracrine mechanisms.
authors.affiliation: The Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.forename: C
authors.initials: C
authors.lastname: Sakamoto
authors.forename: K
authors.initials: K
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.forename: H
authors.initials: H
authors.lastname: Noguchi
authors.forename: H
authors.initials: H
authors.lastname: Mizuno
authors.forename: T
authors.initials: T
authors.lastname: Akamatsu
authors.forename: M
authors.initials: M
authors.lastname: Kasuga
mesh_terms: D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000077214:Becaplermin; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D006224:Cricetinae; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis; D066246:ErbB Receptors / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000503:physiopathology; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D017077:Culture Media, Conditioned; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D004247:DNA; D066246:ErbB Receptors