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波形蛋白2增强肝星状细胞在结直肠癌肝转移中的活性。

WAVE2 Enhanced Hepatic Stellate Cells Activity in Colorectal Liver Metastases.

作者信息

Tan Fengbo, He Dongren, Hu Kuan, Wang Dong, Zhang Sai, Li Juanni, Wang Zhiming, Tao Yiming

机构信息

Department of General Surgery Research, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Aug 24;12:7671-7680. doi: 10.2147/CMAR.S259125. eCollection 2020.

DOI:10.2147/CMAR.S259125
PMID:32904432
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7455535/
Abstract

BACKGROUND

Cancer cell migration, tumor angiogenesis, and activated hepatic stellate cells (a-HSCs) promote the development of colorectal liver metastases (CLM). Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 (WAVE2) has been associated with CLM, although the underlying molecular mechanisms remain unclear.

METHODS

In the current study, we evaluated the relationship between WAVE2 and CLM in 103 CLM patients who underwent liver resection. Immunohistochemistry (IHC) staining was performed to determine the association between WAVE2 protein expression and hepatic micro-metastasis in human CLM tissues. WAVE2 knockout was performed in hepatic stellate cells (HSC) to explore the function and signaling pathways of WAVE2 in colorectal cancer progression.

RESULTS

Significantly higher levels of WAVE2 were detected in portal-associated relative to sinusoid-associated micro-metastasis. A strong correlation was identified between WAVE2 levels and microvessel density (MVD) in hepatic metastasis. Similarly, expression of WAVE2 was closely associated with activation of HSCs. Mechanistically, WAVE2 regulated the progression of human CLM acts by regulating the growth factor β (TGF-β) and Hippo pathways via effector yes-associated protein (YAP1).

CONCLUSION

Overall, our results demonstrated that WAVE2 participates in CLM tumor microenvironment, and can be a potential latent therapeutic target for CLM.

摘要

背景

癌细胞迁移、肿瘤血管生成以及活化的肝星状细胞（a-HSCs）促进了结直肠癌肝转移（CLM）的发展。威斯科特-奥尔德里奇综合征蛋白家族维普洛林同源蛋白2（WAVE2）与CLM有关，但其潜在的分子机制仍不清楚。

方法

在本研究中，我们评估了103例行肝切除术的CLM患者中WAVE2与CLM之间的关系。采用免疫组织化学（IHC）染色来确定WAVE2蛋白表达与人类CLM组织中肝微转移之间的关联。在肝星状细胞（HSC）中进行WAVE2基因敲除，以探索WAVE2在结直肠癌进展中的功能和信号通路。

结果

相对于窦状隙相关微转移，在门静脉相关微转移中检测到的WAVE2水平显著更高。在肝转移中，WAVE2水平与微血管密度（MVD）之间存在强烈相关性。同样，WAVE2的表达与HSCs的活化密切相关。从机制上讲，WAVE2通过效应器Yes相关蛋白（YAP1）调节生长因子β（TGF-β）和Hippo通路来调控人类CLM的进展。

结论

总体而言，我们的结果表明WAVE2参与了CLM肿瘤微环境，并且可能是CLM的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/f7cbc11b9de2/CMAR-12-7671-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/1afb77e2c1ae/CMAR-12-7671-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/98c2d5d990dd/CMAR-12-7671-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/2687dd1fa275/CMAR-12-7671-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/3915ca0e5665/CMAR-12-7671-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/f7cbc11b9de2/CMAR-12-7671-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/1afb77e2c1ae/CMAR-12-7671-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/98c2d5d990dd/CMAR-12-7671-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/2687dd1fa275/CMAR-12-7671-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/3915ca0e5665/CMAR-12-7671-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/7455535/f7cbc11b9de2/CMAR-12-7671-g0005.jpg

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