Department of Medical Technology, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Chuou-ku, Sagamihara, Kanagawa 252-5201, Japan.
Anticancer Res. 2011 Jul;31(7):2493-7.
Monocytes are known to differentiate into tissue-specific macrophages in response to the tissue environment, and it has been suggested that tumor-associated macrophages might promote angiogenesis. Therefore, the factors associated with monocyte differentiation into tumor-associated macrophages may become new targets for cancer therapy. However, these factors remain unclear in human colon cancer. The aim of this study was to identify the factors associated with human monocyte differentiation into tumor-associated macrophages at human colon cancer sites.
A human monocyte cell line (THP-1) was co-cultured with a human colon cancer cell line (DLD-1) and mRNA expression was analyzed by quantitative real-time PCR.
In THP-1 cells, monocyte chemotactic protein (MCP)-1 mRNA expression increased in a time-dependent manner from day 3 after co-culture with DLD-1 cells; furthermore, expression of vascular endothelial growth factor (VEGF)-A, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-8 mRNA was increased from day 5. This increase in mRNA expression in the THP-1 cells was attributable to the presence of the DLD-1 cells. Therefore, MCP-1, VEGF-A, TNF-α, IL-1β, and IL-8 are suggested to be associated with differentiation of human monocytes into tumor-associated macrophages at human colon cancer sites.
已知单核细胞会在组织环境的作用下分化为组织特异性巨噬细胞，并且有人提出肿瘤相关巨噬细胞可能促进血管生成。因此，与单核细胞分化为肿瘤相关巨噬细胞相关的因素可能成为癌症治疗的新靶点。然而，这些因素在人类结肠癌中尚不清楚。本研究的目的是鉴定与人类结肠癌部位的单核细胞分化为肿瘤相关巨噬细胞相关的因素。
将人单核细胞系（THP-1）与人结肠癌细胞系（DLD-1）共培养，并通过定量实时 PCR 分析 mRNA 表达。
在 THP-1 细胞中，与 DLD-1 细胞共培养 3 天后，单核细胞趋化蛋白（MCP）-1 mRNA 表达呈时间依赖性增加；此外，从第 5 天开始，血管内皮生长因子（VEGF）-A、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和 IL-8 的 mRNA 表达增加。THP-1 细胞中这种 mRNA 表达的增加归因于 DLD-1 细胞的存在。因此，MCP-1、VEGF-A、TNF-α、IL-1β 和 IL-8 被认为与人类单核细胞在人类结肠癌部位分化为肿瘤相关巨噬细胞有关。
