Tumor-Associated Macrophage-Induced Invasion and Angiogenesis of Human Basal Cell Carcinoma Cells by Cyclooxygenase-2 Induction
Tumor-Associated Macrophage-Induced Invasion and Angiogenesis of Human Basal Cell Carcinoma Cells by Cyclooxygenase-2 Induction
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DOI：
10.1038/jid.2008.310
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发表时间：
2009-04-01
影响因子：
6.5
通讯作者：
Jee, Shiou-Hwa
中科院分区：
文献类型：
--
作者：
Tjiu, Jeng-Wei;Chen, Jau-Shiuh;Jee, Shiou-Hwa
肿瘤相关巨噬细胞 (TAM) 和环氧合酶-2 (COX-2) 与许多人类癌症的侵袭、血管生成和不良预后相关。然而，TAM 在人类基底细胞癌 (BCC) 中的作用仍然难以捉摸。我们发现浸润肿瘤的 TAM 数量与人 BCC 细胞中的浸润深度、微血管密度和 COX-2 表达相关。 TAM 也在表达 COX-2 的 BCC 肿瘤巢附近聚集。我们假设 TAM 可能激活 BCC 细胞中的 COX-2，随后增加其侵袭和血管生成。 TAM 是一种 M2 巨噬细胞，源自暴露于 Th2 细胞因子的巨噬细胞。将源自外周血单核细胞的 M2 极化巨噬细胞与 BCC 细胞共培养，无需直接接触。与 M2 巨噬细胞共培养可诱导 BCC 细胞依赖 COX-2 的侵袭和血管生成。人 THP-1 细胞系细胞经佛波醇肉豆蔻酸酯醋酸酯 (PMA) 处理后，分化为具有 M2 功能谱的巨噬细胞。与 PMA 处理的 THP-1 巨噬细胞共培养可诱导 COX-2 依赖性基质金属蛋白酶 9 的释放，并随后增加 BCC 细胞的侵袭。巨噬细胞还诱导 COX-2 依赖性碱性成纤维细胞生长因子和血管内皮生长因子-A 的分泌，并增加 BCC 细胞中的血管生成。
Tumor-associated macrophages (TAMs) and cyclooxygenase-2 (COX-2) are associated with invasion, angiogenesis, and poor prognosis in many human cancers. However, the role of TAMs in human basal cell carcinoma (BCC) remains elusive. We found that the number of TAMs infiltrating the tumor is correlated with the depth of invasion, microvessel density, and COX-2 expression in human BCC cells. TAMs also aggregate near COX-2 expressing BCC tumor nests. We hypothesize that TAMs might activate COX-2 in BCC cells and subsequently increase their invasion and angiogenesis. TAMs are a kind of M2 macrophage derived from macrophages exposed to Th2 cytokines. M2-polarized macrophages derived from peripheral blood monocytes were cocultured with BCC cells without direct contact. Coculture with the M2 macrophages induced COX-2-dependent invasion and angiogenesis of BCC cells. Human THP-1 cell line cells, after treated with phorbol myristate acetate (PMA), differentiated to macrophages with M2 functional profiles. Coculture with PMA-treated THP-1 macrophages induced COX-2-dependent release of matrix metalloproteinase-9 and subsequent increased invasion of BCC cells. Macrophages also induced COX-2-dependent secretion of basic fibroblast growth factor and vascular endothelial growth factor-A, and increased angiogenesis in BCC cells.