Department of Breast Care Surgery, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, China.
School of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou, China.
J Immunother. 2024;47(9):369-377. doi: 10.1097/CJI.0000000000000518. Epub 2024 Apr 17.
Taurine (Tau) has been found to inhibit triple-negative breast cancer (TNBC) invasion and metastasis. However, its effect on tumor-promoting macrophages and tumor suppressor macrophages in breast cancer progression remains unknown. In this study, we investigated the effects of Tau on macrophage polarization and its role in TNBC cell growth, invasion, and metastasis. We induced human THP-1 monocytes to differentiate into M2 macrophages through exogenous addition of interleukin-4. We used the TNBC cell lines MDA-MB-231 and BT-549 cultured in a conditioned medium from M2 macrophages to investigate the effect of Tau on tumor growth and invasion. We analyzed macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression by quantitative polymerase chain reaction. We also detected the PTEN-PI3K/Akt/mTOR signaling pathway that mediates M1 macrophage to suppress tumor invasion using western blotting. Our results showed that Tau inhibits breast cancer metastasis to the lungs in vivo and cell invasion by altering the polarization of tumor-associated macrophage in vitro. In addition, Tau can up-regulate PTEN expression, suppress the PI3K-Akt signaling pathway, and promote the M1 polarization of macrophages, which ultimately inhibits the metastasis of TNBC cells. Our findings suggest that Tau inhibits the activation of the PI3K-Akt-mTOR signaling pathway by up-regulating PTEN , promotes the proportion of M1 macrophages in tumor-associated macrophage, and suppresses the invasion and metastasis of TNBC. This provides a potential therapeutic approach to influence cancer progression and metastasis.
牛磺酸（Tau）已被发现可抑制三阴性乳腺癌（TNBC）的侵袭和转移。然而，其对乳腺癌进展过程中促肿瘤巨噬细胞和肿瘤抑制巨噬细胞的影响尚不清楚。在本研究中，我们研究了 Tau 对巨噬细胞极化的影响及其在 TNBC 细胞生长、侵袭和转移中的作用。我们通过外源性添加白细胞介素 4 诱导人 THP-1 单核细胞分化为 M2 巨噬细胞。我们使用 M2 巨噬细胞条件培养基培养的 TNBC 细胞系 MDA-MB-231 和 BT-549 来研究 Tau 对肿瘤生长和侵袭的影响。我们通过定量聚合酶链反应分析了巨噬细胞亚群分布、M1 和 M2 巨噬细胞相关标志物以及 mRNA 表达。我们还使用 Western blot 检测了介导 M1 巨噬细胞抑制肿瘤侵袭的 PTEN-PI3K/Akt/mTOR 信号通路。我们的结果表明，Tau 通过改变体外肿瘤相关巨噬细胞的极化来抑制体内乳腺癌向肺部转移和细胞侵袭。此外，Tau 可以上调 PTEN 表达，抑制 PI3K-Akt 信号通路，并促进巨噬细胞的 M1 极化，最终抑制 TNBC 细胞的转移。我们的研究结果表明，Tau 通过上调 PTEN 抑制 PI3K-Akt-mTOR 信号通路的激活，促进肿瘤相关巨噬细胞中 M1 巨噬细胞的比例，抑制 TNBC 的侵袭和转移。这为影响癌症进展和转移提供了一种潜在的治疗方法。
