乳腺癌来源的 CAV1 通过调节整合素 α6β4 以及肿瘤相关中性粒细胞的招募和极化促进肺转移。

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
International Journal of Biological Sciences Pub Date : 2024-10-14 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.94153
Qing Lin, Siwen Zong, Yi Wang, Youjia Zhou, Keqin Wang, Fuxiu Shi, Jiayang Wang, Mingrui Feng, Wenting Luo, Lifang Zhang, Hui Lin, Lixia Xiong
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引用次数: 0

摘要

乳腺癌(BC)患者的肺转移是其死亡率高的主要原因之一。研究发现,乳腺癌最常见的细胞外小泡(sEVs)受体--整合素α6β4与肺上皮细胞中的表面活性物质相关蛋白(SFTPC)相互作用,使乳腺癌更容易转移到肺部。肿瘤相关中性粒细胞(TANs)作为肺转移前生态位(PMN)的组成部分,在BC肺转移中扮演着至关重要的角色,具有两面性。有研究表明,Toll样受体4(Toll-like Receptor4,TLR4)可参与NF-B和NLRP3等信号转导,促进肿瘤转移。一种名为洞穴素-1(CAV1)的细胞膜结构蛋白与 BC 的增殖、转移和免疫控制有关。根据我们之前的研究,BC衍生的sEVs上的CAV1通过增强肺成纤维细胞中tenascin-C(TnC)的分泌来促进ECM的沉积,通过增加肺上皮细胞中PMN标记基因和炎性趋化因子的表达,以及通过抑制PTEN/CCL2/VEGF-A轴来支持肺巨噬细胞的N2型极化,从而促进肺PMN的形成。要确定 sEVs 介导的 CAV1 如何促进 BC 向肺部转移,还需要更多的研究。通过创建稳定干扰 CAV1 的稳定转移细胞系和 BC 肺转移小鼠模型,我们研究了 sEVs 介导的 CAV1 如何促进 BC 肺转移以及 TAN 在体内和体外的招募和极化。在这项研究中,我们发现CAV1通过控制整合素α6β4的表达,以及通过激活TLR4-NF-B-IL-6/CCL2和TLR4/NF-B/NLRP3信号通路来促进TANs的招募和极化,从而增加了BC肺转移发生的可能性。根据我们的研究结果,CAV1能调节整合素α6β4和TLR4信号转导,而这两种信号转导对BC肺转移至关重要。这一发现可能会为预防和治疗卡介苗肺转移开辟新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Breast cancer-derived CAV1 promotes lung metastasis by regulating integrin α6β4 and the recruitment and polarization of tumor-associated neutrophils.

Lung metastasis in breast cancer (BC) patients is one of the main reasons for their high mortality rate. The most prevalent BC small extracellular vesicles (sEVs receptor, integrin α6β4, has been found to interact with surfactant-associated protein (SFTPC) in lung epithelial cells, making BC more likely to metastasize to the lung. Tumor-associated neutrophils (TANs) play an essential role in BC lung metastasis as a component of the lung pre-metastatic niche (PMN) with two sides. It has been demonstrated that Toll-like Receptor4 (TLR4) can participate in signaling, such as NF-B and NLRP3, to facilitate tumor metastasis. A cellular membrane structural protein called caveolin-1 (CAV1) is associated with BC's proliferation, metastasis, and immunological control. According to our previous research, CAV1 on BC-derived sEVs facilitates the formation of the lung PMN by enhancing tenascin-C (TnC) secretion in lung fibroblasts to promote the deposition of ECM, by increasing the expression of PMN marker genes and inflammatory chemokines in lung epithelial cells, and by supporting N2-type polarization of lung macrophages via inhibiting the PTEN/CCL2/VEGF-A axis. More research is needed to determine how sEVs-mediated CAV1 facilitates BC-targeted metastasis to the lungs. By creating a stable-translocating cell line that stably interfered with CAV1 and a mouse model of BC lung metastasis, we investigated how sEVs-mediated CAV1 promotes BC lung metastasis and TAN recruitment and polarization in vivo and in vitro. In this study, we showed that CAV1 increases the likelihood that BC lung metastasis would occur by controlling the expression of integrin α6β4 and via boosting TANs recruitment and polarization through activating the TLR4-NF-B-IL-6/CCL2 and TLR4/NF-B/NLRP3 signaling pathways. According to our findings, CAV1 regulates integrin α6β4 and modulates TLR4 signaling, both of which are critical for BC lung metastasis. This finding may open new avenues for BC lung metastasis prevention and treatment.

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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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