Blockade of exosome generation by GW4869 inhibits the education of M2 macrophages in prostate cancer.
Blockade of exosome generation by GW4869 inhibits the education of M2 macrophages in prostate cancer.
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GW4869 阻断外泌体生成可抑制前列腺癌中 M2 巨噬细胞的培养
DOI：
10.1186/s12865-022-00514-3
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发表时间：
2022-08-08
期刊：
影响因子：
3
通讯作者：
中科院分区：
文献类型：
--
作者：
肿瘤相关巨噬细胞被认为是影响肿瘤发展的主要因素。近年来，大量的研究表明，肿瘤细胞能够通过递送大量的外切体来培养其微环境，然而，来自PCa细胞的外切体在巨噬细胞极化中的作用机制尚不清楚。因此，我们试图确定外切体生物发生的抑制剂GW4869阻断外切体的生成是否会阻碍巨噬细胞分化为M2细胞。在本研究中，我们首先使用MagCapture™Exosome分离试剂盒PS从无外切体血清培养的PCa细胞上清液中获得外切体，然后观察它们对巨噬细胞的影响。我们的数据证实，前列腺癌细胞释放的外切体可以诱导巨噬细胞分化为M2细胞。从机制上讲，外切体通过激活AKT和STAT3信号通路对巨噬细胞发挥作用。重要的是，GW4869显著抑制了前列腺癌细胞外切体的释放，并进一步损害了巨噬细胞的M2分化及其促肿瘤活性。我们还证实了GW4869能够抑制M2巨噬细胞的培养，从而抑制体内前列腺癌的发展。综上所述，我们的研究结果表明，GW4869作为一种肿瘤外切体分泌的抑制因子，可能在前列腺癌的转移治疗中发挥重要作用。网上版载有补充材料，可在10.1186/s12865-022-00514-3查阅。
Tumor-associated macrophages are considered to be a major contributor affecting the development of tumors. Recently, numerous studies have shown that tumor cells were able to educate their microenvironment by delivering a significant amount of exosomes, however, the mechanism that exosomes from PCa cells work in macrophage polarization remains obscure. Therefore, we sought to determine whether blockade of exosome generation by GW4869, an inhibitor of exosome biogenesis, would impede macrophages from differentiating into M2 cells. In this study, we first obtained exosomes from the supernatant media of PCa cells cultured with exosome-free serum using the Magcapture™ Exosome Isolation Kit PS, and then investigated their effects on macrophages. Our data confirmed that exosomes released by prostate cancer cells can induce macrophages to differentiate into M2 cells. Mechanistically speaking, exosomes exert their effects on macrophages through activating the AKT and STAT3 signaling pathways. Importantly, treatment with GW4869 significantly inhibited the release of exosomes from PCa cells, and further impaired M2 differentiation of macrophages and their pro-tumor activity. We also demonstrated that GW4869 was able to inhibit the education of M2 macrophages, and then inhibit the progression of prostate cancer in vivo. In brief, our findings indicated that GW4869 impeded the PCa exosome-induced M2 differentiation of macrophages and the progression of prostate cancer, suggesting that GW4869 could play an important role in the treatment of prostate cancer metastasis as an inhibitor of tumor exosome secretion. The online version contains supplementary material available at 10.1186/s12865-022-00514-3.
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DOI：
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发表时间：
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期刊：
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DOI：
10.1016/j.bbadis.2015.08.010
发表时间：
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期刊：
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影响因子：
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