Gastric epithelial cells secrete a PDGF-like peptide, a potent mitogen for human gastric fibroblasts.
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.
Wada
K
K
The Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Sakamoto
C
C
Matsuda
K
K
Uchida
T
T
Noguchi
H
H
Mizuno
H
H
Akamatsu
T
T
Kasuga
M
M
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
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