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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
Source :
Journal of Experimental & Clinical Cancer Research, Vol 39, Iss 1, Pp 1-14 (2020)
Publication Year :
2020
Publisher :
BMC, 2020.

Abstract

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-CreERT2 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.

Details

Language :
English
ISSN :
17569966
Volume :
39
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Experimental & Clinical Cancer Research
Publication Type :
Academic Journal
Accession number :
edsdoj.7423c926774844cb9a4965eec257e2c6
Document Type :
article
Full Text :
https://doi.org/10.1186/s13046-020-01630-x