The Emerging Roles of Pericytes in Modulating Tumor Microenvironment.

Ruipu Sun,Xiangzhan Kong,Xiaoyi Qiu,Ping-Pui Wong,Cheng Huang

doi:10.3389/fcell.2021.676342

Ruipu Sun, Xiangzhan Kong + Show 3 more

Open Access

https://doi.org/10.3389/fcell.2021.676342

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Abstract

Pericytes (PCs), known as mural cells, play an important blood vessel (BV) supporting role in regulating vascular stabilization, permeability and blood flow in microcirculation as well as blood brain barrier. In carcinogenesis, defective interaction between PCs and endothelial cells (ECs) contributes to the formation of leaky, chaotic and dysfunctional vasculature in tumors. However, recent works from other laboratories and our own demonstrate that the direct interaction between PCs and other stromal cells/cancer cells can modulate tumor microenvironment (TME) to favor cancer growth and progression, independent of its BV supporting role. Furthermore, accumulating evidence suggests that PCs have an immunomodulatory role. In the current review, we focus on recent advancement in understanding PC’s regulatory role in the TME by communicating with ECs, immune cells, and tumor cells, and discuss how we can target PC’s functions to re-model TME for an improved cancer treatment strategy.

Highlights

Pericytes (PCs) are embedded in the basement membrane of blood microvessels (Bergers and Song, 2005), which play a vital role in regulating physiological and pathological events, including vascular development, homeostasis, fibrosis, and stroke
Recent work from our laboratory shows that PC can regulate tumor cell growth via paracrine signals controlled by β3-integrin (Wong et al, 2020), independent of its blood vessel (BV) supporting function, suggesting that its regulatory role in the tumor microenvironment (TME) is far more complicated than we previously thought
Clinical studies show that high BV’s PC coverage is associated with increased tumor growth and poor prognosis (Furuhashi et al, 2004), while it is correlated with reduced distant metastasis in colorectal cancer patients (Yonenaga et al, 2005). These findings suggest that PC overabundance and deficiency occur in different tumor types during vascularization with mixed clinical outcome, implying that targeting PC coverage may not be an ideal strategy for anti-cancer treatment

Summary

Introduction

Pericytes (PCs) are embedded in the basement membrane of blood microvessels (Bergers and Song, 2005), which play a vital role in regulating physiological and pathological events, including vascular development, homeostasis, fibrosis, and stroke. It is important to investigate the underlying role of PCs in modulating tumor angiogenesis and TME in order to develop an improved anti-cancer treatment.

Results

Conclusion