Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer.

作者：Takayuki Ueno, Masakazu Toi, Hisashi Saji, Mariko Muta, Hiroko Bando, Katsumasa Kuroi, Morio Koike, Hidekuni Inadera, Kouji Matsushima · 发表于：PubMed · 年份：2000 · 被引用次数：711 · 研究领域：Chemokine receptors and signaling、Immune cells in cancer、Angiogenesis and VEGF in Cancer

Tumor cells stimulate the formation of stroma that secretes various mediators pivotal for tumor growth, including growth factors, cytokines, and proteases. However, little is known about the local regulation of these soluble mediators in the human tumor microenvironment. In this study, the local expression of cytokines, chemokines, and angiogenic factors was investigated in primary breast cancer tissue. The concentrations of interleukin (IL)-1, IL-4, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-alpha, IFN-gamma, IL-8, macrophage chemoattractant protein (MCP)-1, epithelial-neutrophil activating peptide-78, vascular endothelial growth factor, and thymidine phosphorylase (TP) were measured in 151 primary breast cancer extracts by ELISA. Tumor-associated macrophages (TAMs) were also examined by immunohistochemistry with anti-CD68 antibodies. The correlation between soluble mediators and the relationship between TAM count and soluble mediators were evaluated. MCP-1 concentration was correlated significantly with the level of vascular endothelial growth factor, TP, TNF-alpha, and IL-8, which are potent angiogenic factors. IL-4 concentration was correlated significantly with IL-8 and IL-10. On the other hand, an inverse association was observed between TP and IL-12. The level of MCP-1 was associated significantly with TAM accumulation. In the immunohistochemical analysis, MCP-1 expression was observed in both infiltrating macrophages and tumor cells. Prognostic analysis revealed ...