{"title":"牛磺酸通过 PTEN-PI3K/Akt/mTOR 通路调节巨噬细胞极化抑制三阴性乳腺癌的肺转移","authors":"Yufeng Lin, Yongtong Huang, Yifan Zheng, Wanting Chen, Yongcheng Zhang, Yongxia Yang, Wenbin Huang","doi":"10.1097/CJI.0000000000000518","DOIUrl":null,"url":null,"abstract":"SUMMARY\nTaurine (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.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Taurine Inhibits Lung Metastasis in Triple-Negative Breast Cancer by Modulating Macrophage Polarization Through PTEN-PI3K/Akt/mTOR Pathway.\",\"authors\":\"Yufeng Lin, Yongtong Huang, Yifan Zheng, Wanting Chen, Yongcheng Zhang, Yongxia Yang, Wenbin Huang\",\"doi\":\"10.1097/CJI.0000000000000518\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"SUMMARY\\nTaurine (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. 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引用次数: 0
摘要
摘要已发现牛磺酸(Tau)可抑制三阴性乳腺癌(TNBC)的侵袭和转移。然而,它对乳腺癌进展过程中肿瘤促进巨噬细胞和肿瘤抑制巨噬细胞的影响仍然未知。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。我们使用在M2巨噬细胞条件培养基中培养的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巨噬细胞相关标记物以及mRNA表达。我们还利用Western印迹技术检测了介导M1巨噬细胞抑制肿瘤侵袭的PTEN-PI3K/Akt/mTOR信号通路。我们的研究结果表明,Tau能在体内抑制乳腺癌向肺部的转移,并在体外通过改变肿瘤相关巨噬细胞的极化来抑制细胞侵袭。此外,Tau还能上调PTEN的表达,抑制PI3K-Akt信号通路,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。
Taurine Inhibits Lung Metastasis in Triple-Negative Breast Cancer by Modulating Macrophage Polarization Through PTEN-PI3K/Akt/mTOR Pathway.
SUMMARY
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.
期刊介绍:
Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.