Vascular endothelial growth factor synthesis by human omental mesothelial cells is augmented by fibroblast growth factor-2: possible role of mesothelial cell on the development of peritoneal metastasis.
Although peritoneal metastasis is an important factor determining the prognosis of patients with gastrointestinal cancer, the mechanisms have not yet been clearly defined. Human peritoneal mesothelial cells (HPMC) are the first line against disseminated tumor cells. Recent reports have shown that mesothelial cells are capable of secreting various cytokines and growth factors. In this study, we isolated human mesothelial cells from surgically resected omental tissue and examined the production and interaction of two major angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). Quiescent HPMC produced a considerable amount of VEGF at almost the same level as tumor cells. Interestingly, addition of FGF-2 to the culture significantly increased the mRNA synthesis and protein secretion of VEGF in a dose-dependent manner, as determined by Northern blot and ELISA. The addition of 0.5 ng/mL FGF-2 was enough to stimulate VEGF production, and the effect reached a plateau at 5 ng/mL. Reverse-transcribed polymerase chain reaction (RT-PCR) method clarified that the HPMC-derived VEGF consisted mostly of VEGF(121) and VEGF(165), which are both predominantly soluble forms. These data suggest that HPMC contribute to the development of metastases and the accumulation of malignant ascites due to the production of VEGF, especially in cancers that do not express enough amount of VEGF.
Department of Surgery, Division of Surgical Oncology, The University of Tokyo, Tokyo, Japan. sakou-dis@h.u-tokyo.ac.jp
Akihiro
A
Sako
Joji
J
Kitayama
Hironori
H
Yamaguchi
Shoichi
S
Kaisaki
Hiroyuki
H
Suzuki
Kazuhiko
K
Fukatsu
Shin
S
Fujii
Hirokazu
H
Nagawa
D017398:Alternative Splicing; D015152:Blotting, Northern; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009852:Omentum; D010051:Ovarian Neoplasms / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000556:secondary*; D010537:Peritoneum / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2