乳腺癌微环境中巨噬细胞相关因子与环氧化酶-2的调节

Crosstalk between macrophage-delivered cytokines and cyclooxygenase-2 in breast cancer microenvironment

肿瘤微环境中浸润的巨噬细胞(tumor-associated macrophages,TAMs)是近年来癌症治疗的新靶点。TAMs通过分泌大量促癌细胞因子如血管内皮生长因子、白细胞介素、基质金属蛋白酶等,促进肿瘤细胞增殖、侵袭和转移。炎症因子环氧化酶-2(cyclooxygenase-2,COX-2)参与了微环境中血管形成和免疫调节,加速肿瘤进程,也是乳腺癌治疗的有力靶点。而COX-2抑制剂如塞来昔布,在抑制TAMs活性和改善肿瘤微环境方面具有较大潜力。因此,本文就乳腺癌微环境中TAMs分泌的重要细胞因子与COX-2的相互关系加以讨论,分析其对应的拮抗剂单独或与COX-2抑制剂联合的使用价值,旨在为选择多靶点联合阻断TAMs活性的研究提供理论基础,也为乳腺癌的生物靶向治疗提供新方向。

A new target in cancer treatment involves tumor-associated macrophages （TAMs） which are infiltrated in microenvi-ronment. By secreting a wide range of cancer-promoting cytokines, such as vascular endothelial growth factor, interleukins, and matrix metalloproteinase, TAMs can promote the proliferation, invasion, and metastasis of cancer cells. Cyclooxygenase-2 （COX-2）, an inflam-matory factor that is significant for angiogenesis and immunoregulation within the local microenvironment, may also contribute to can-cer progression and act as a novel target for breast cancer therapy. Several COX-2 inhibitors, such as celecoxib, have shown potential as suppressors of TAMs and the microenvironment. Hence, the current study discusses the crosstalk between TAMs-delivered important cytokines and COX-2 in the breast cancer microenvironment, and then analyzes the value of homologous antagonists alone or in combi-nation with COX-2 inhibitors. This paper aims to provide the theoretical principle of multi-target selection in TAMs blockage, and offer a new direction for biological targeted therapy in breast cancer treatment.