title: Monocyte chemoattractant protein-1 expression correlates with macrophage infiltration and tumor vascularity in human gastric carcinomas.
abstract: The purpose of this study was to investigate the role of interactions between tumor cells and macrophages during angiogenesis in human gastric carcinomas. Macrophage infiltration into tumors and monocyte chemoattractant protein-1 (MCP-1) expression was assessed in 72 archival specimens of gastric carcinoma for comparison with tumor vascularity. The mRNA expression of MCP-1 was examined by RT-PCR in 6 gastric carcinoma cell lines and in fresh biopsy specimens from 18 patients. Immunolocalization of representative angiogenic factors, vascular endothelial growth factor (VEGF), and platelet-derived endothelial cell growth factor (PD-ECGF) was also done. MCP-1 expression in tumor cells increased with the depth of tumor invasion (Tis 9.5%, T1 19.4%, T2-4 60.0%), as did microvessel density and macrophage infiltration. Macrophage counts correlated with vessel counts, and both were significantly higher in MCP-1-positive than in negative tumors. Of the 6 gastric carcinoma cell lines, 2 constitutively expressed MCP-1 mRNA. In 6 (33.3%) of 18 biopsy samples, MCP-1 mRNA was expressed at higher levels in tumor tissues than in normal mucosa. VEGF protein was expressed by gastric carcinoma cells, whereas PD-ECGF protein was expressed mainly by stromal mononuclear cells. MCP-1 expression correlated significantly with VEGF but not PD-ECGF expression in gastric carcinomas. These results suggest that MCP-1 produced by human gastric carcinoma cells plays a role in angiogenesis via macrophage recruitment and activation.
authors.affiliation: Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohta
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kitadai
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yoshihara
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
authors.forename: Naofumi
authors.initials: N
authors.lastname: Mukaida
authors.forename: Ken
authors.initials: K
authors.lastname: Haruma
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D002277:Carcinoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D013939:Thymidine Phosphorylase / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D018932:Chemokine CCL2; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D013939:Thymidine Phosphorylase