Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, Heilongjiang, China.
Neoplasma. 2021 Sep;68(5):938-946. doi: 10.4149/neo_2021_201226N1404. Epub 2021 Jun 17.
Breast cancer is the most common malignancy in females. The emergence of endocrine resistance is frustrating for estrogen receptor (ER)-positive breast cancer patients even the efficacy of endocrine therapy is acceptable. Our previous study has shown that tumor-associated macrophages (TAMs) are associated with endocrine resistance, yet the mechanism remains unclear. This article is dedicated to discuss the role of TAMs in the endocrine resistance of breast cancer. It was found that tamoxifen-resistant MCF-7 cells induced more macrophages polarized into TAMs. Conversely, TAMs increased the expression of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), which promoted tamoxifen resistance through the activation of the PI3K/Akt/mTOR signaling pathway in MCF-7 cells. Furthermore, clinical analysis supported that five-year progression-free survival (PFS) of breast cancer patients with abundant COX-2 expression in TAMs was shorter (p<0.05). Therefore, these results show a positive feedback loop between TAMs and breast cancer cells, suggesting that TAMs and COX-2 may be new therapeutic targets for breast cancer patients suffering from endocrine resistance.
乳腺癌是女性最常见的恶性肿瘤。即使内分泌治疗的疗效可以接受，内分泌抵抗的出现也令雌激素受体（ER）阳性乳腺癌患者感到沮丧。我们之前的研究表明，肿瘤相关巨噬细胞（TAMs）与内分泌抵抗有关，但具体机制尚不清楚。本文旨在探讨 TAMs 在乳腺癌内分泌抵抗中的作用。研究发现，他莫昔芬耐药 MCF-7 细胞诱导更多的巨噬细胞极化为 TAMs。相反，TAMs 增加了环氧化酶-2（COX-2）/前列腺素 E2（PGE2）的表达，通过 MCF-7 细胞中 PI3K/Akt/mTOR 信号通路的激活促进了他莫昔芬耐药。此外，临床分析支持 TAMs 中 COX-2 表达丰富的乳腺癌患者五年无进展生存（PFS）较短（p<0.05）。因此，这些结果表明 TAMs 和乳腺癌细胞之间存在正反馈循环，提示 TAMs 和 COX-2 可能成为内分泌抵抗乳腺癌患者的新治疗靶点。
