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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2020 | Research

SM22α⁺ vascular mural cells are essential for vessel stability in tumors and undergo phenotype transition regulated by Notch signaling

Authors: Xinxin Zhang, Xianchun Yan, Jing Cao, Ziyan Yang, Xiuli Cao, Yufei Zhang, Liang Liang, Minhua Zheng, Xiaowei Liu, Jian Zhang, Hua Han

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2020

Abstract

Background

Malformation of blood vessels represents a hallmark of cancers, but the role and regulation of vascular mural cells (vMCs), including vascular smooth muscle cells (vSMCs) and pericytes, in tumors has not been fully understood. SM22α has been identified as a marker of vSMCs. This study aims at elucidating the function and regulation of SM22α⁺ mural cells (SM22-MCs) in tumor stroma.

Methods

Gene-modified mice with a SM22α-CreER^T2 transgene were employed to deplete SM22-MCs or activate/block Notch signaling in these cells. vSMCs from mouse dorsal aorta (vSMCs-DA) were cultured in vitro. RNA-seq was used to compare gene expression profiles. qRT-PCR and western blotting were used to determine gene expression level. Immunofluorescence was used to observe morphological alterations in tumors.

Results

SM22-MCs are essential for stabilizing tumor vasculature. Notch signaling was downregulated in tumor-derived SM22-MCs and vSMCs-DA treated with cancer cell-derived conditioned medium. Notch activation in SM22-MCs normalized tumor vasculature and repressed tumor growth. On the other hand, Notch disruption aggravated abnormal tumor vasculature and promoted growth and metastasis. Gene expression profiling of vSMCs-DA showed that Notch activation enhances their contractile phenotype and suppresses their secretory phenotype, further attenuating the invasion and proliferation of tumor cells. In contrast, Notch blockade in vSMCs-DA mitigated their contractile phenotype while strengthened the secretory phenotype.

Conclusion

SM22-MCs facilitate vessel stability in tumors, and they gain a secretory phenotype and promote tumor malignancy in the absence of Notch signaling.

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Title: SM22α+ vascular mural cells are essential for vessel stability in tumors and undergo phenotype transition regulated by Notch signaling
Authors: Xinxin Zhang
Xianchun Yan
Jing Cao
Ziyan Yang
Xiuli Cao
Yufei Zhang
Liang Liang
Minhua Zheng
Xiaowei Liu
Jian Zhang
Hua Han
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2020
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-020-01630-x

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Abstract

Background

Methods

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