CD133-containing microvesicles promote cancer progression by inducing M2-like tumor-associated macrophage polarization in the tumor microenvironment of colorectal cancer.

IF 3.3 3区 医学 Q2 ONCOLOGY
Sang Yun Kim, Sungyeon Park, Suhyun Kim, Jesang Ko
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引用次数: 0

Abstract

Tumor-associated macrophages (TAMs) are among the most abundant cell types in the tumor microenvironment (TME). The immunosuppressive TME formed by TAMs is an essential prerequisite for cancer progression. Tumor-derived microvesicles (MVs), a subtype of extracellular vesicle shed directly from the plasma membrane, are important regulators of intercellular communication and TME modulation during tumorigenesis. However, the exact mechanism by which tumor-derived MVs induce the generation of the immunosuppressive TME and polarization of TAMs remains unclear. Here, we investigated the role of CD133-containing MVs derived from colorectal cancer (CRC) cells in macrophage polarization and cancer progression. CD133-containing MVs from CRC cells were incorporated into macrophages, and M0 macrophages were morphologically transformed into M2-like TAMs. CD133-containing MVs were found to increase the mRNA expression of M2 macrophage markers. Additionally, cytokine array analysis revealed that M2-like TAMs induced by CD133-containing MVs increased the secretion of interleukin 6, which activated the STAT3 pathway in CRC cells. Furthermore, the conditioned medium of M2-like TAMs promoted cell motility, epithelial-mesenchymal transition, and cell proliferation. However, MVs from CD133-knockdown cells had little effect on TAM polarization and CRC progression. These results demonstrate that CD133-containing MVs induce M2-like TAM polarization and contribute to cancer progression by mediating crosstalk between tumor cells and TAMs in the TME of CRC.

含 CD133 的微囊泡通过诱导结直肠癌肿瘤微环境中的 M2 类肿瘤相关巨噬细胞极化来促进癌症进展。
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境(TME)中最丰富的细胞类型之一。由 TAMs 形成的具有免疫抑制作用的 TME 是癌症进展的重要前提。肿瘤衍生的微囊泡(MVs)是直接从质膜上脱落的细胞外囊泡的一种亚型,是肿瘤发生过程中细胞间通讯和肿瘤微环境调控的重要调节因子。然而,肿瘤衍生的微囊诱导产生免疫抑制性 TME 和 TAMs 极化的确切机制仍不清楚。在这里,我们研究了来自结直肠癌(CRC)细胞的含 CD133 的中空膜在巨噬细胞极化和癌症进展中的作用。来自 CRC 细胞的含 CD133 的 MVs 被纳入巨噬细胞,M0 巨噬细胞在形态上转化为 M2 样 TAMs。研究发现,含CD133的MV可增加M2巨噬细胞标志物的mRNA表达。此外,细胞因子阵列分析表明,含 CD133 的中空膜诱导的 M2 样 TAM 增加了白细胞介素 6 的分泌,而白细胞介素 6 激活了 CRC 细胞中的 STAT3 通路。此外,M2 样 TAMs 的条件培养基还能促进细胞运动、上皮-间质转化和细胞增殖。然而,CD133敲除细胞的MV对TAM极化和CRC进展几乎没有影响。这些结果表明,含CD133的MV可诱导M2样TAM极化,并通过介导肿瘤细胞与TAM之间在CRC的TME中的串联作用而促进癌症进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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