The roles of mesenchymal stem cells in tumor inflammatory microenvironment

Zhao Sun,Robert Chunhua Zhao,Shihua Wang

doi:10.1186/1756-8722-7-14

Abstract

Tumor behavior is not entirely determined by tumor cells. Studies have demonstrated that a variety of non-tumor cells in the tumor microenvironment affect tumor behavior; thus, a new focus of cancer research has been the development of novel cancer treatment ideas and therapeutic targets based on the effects of these cells. Mesenchymal stem cells (MSCs) are an important component of the tumor microenvironment; however, previous studies have produced controversial results regarding whether MSCs promote or inhibit tumor growth and progression. In particular, Naïve MSCs and tumor-derived MSCs (T-MSCs) have different functions. Naïve MSCs could exert bidirectional effects on tumors because these cells can both promote and inhibit tumor progression while T-MSCs promote tumor progression due to influences from the tumor itself and from the inflammatory tumor microenvironment. As an unhealed wound, tumor produces a continuous source of inflammatory mediators and causes aggregation of numerous inflammatory cells, which constitute an inflammatory microenvironment. Inflammatory factors can induce homing of circulating MSCs and MSCs in adjacent tissues into tumors, which are then being “educated” by the tumor microenvironment to support tumor growth. T-MSCs could recruit more immune cells into the tumor microenvironment, increase the proportion of cancer stem cells and promote tumor angiogenesis, further supporting tumor progression. However, as plasticity is a fundamental feature of MSCs, MSCs can also inhibit tumors by activating various MSC-based signaling pathways. Studies of the mechanisms by which interactions among tumors, MSCs, and the inflammatory microenvironment occur and methods to disrupt these interactions will likely reveal new targets for cancer therapy.

Highlights

In 2000, Hanahan and Weinberg summarized the hallmarks of cancer, which included the following capabilities: self-sufficiency with regard to growth signals, apoptosis evasion, insensitivity to anti-growth signals, sustained angiogenesis, tissue invasion & metastasis, and a limitless replicative potential [1]
An in vivo study by Kidd et al found that the fibroblast activation protein (FAP)+ and fibroblast-specific protein (FSP)+ Tumor related fibroblasts (TAF) cells in tumor tissues were mainly derived from bone marrow Mesenchymal stem cell (MSC), whereas vascular endothelial cells in tumor tissues were largely derived from nearby adipose tissues [26]
In a mouse model of ovarian cancer, MSCTLR4 did not promote tumor growth and metastasis. These results indicate that MSCs could be converted to a phenotype that is detrimental to tumor progression

Summary

Introduction

In 2000, Hanahan and Weinberg summarized the hallmarks of cancer, which included the following capabilities: self-sufficiency with regard to growth signals, apoptosis evasion, insensitivity to anti-growth signals, sustained angiogenesis, tissue invasion & metastasis, and a limitless replicative potential [1]. MSC membranes express receptors for a number of different growth factors and inflammatory cytokines, and MSCs exhibit plasticity; in different microenvironments or under different induction conditions, MSCs can differentiate into cells of various types or functions that play different roles in tumor development. There are certain differences in the outcomes produced in tumor tissues by MSCs derived from these two sources Tumors and their microenvironments induce MSC homing through mechanisms that depend mainly on various inflammatory cytokines, chemokines, growth factors, and other factors (Figure 1). TAFs isolated from tumors or tumor-conditioned medium-induced myofibroblasts promote tumor growth, whereas myofibroblast-like cells derived from 5-azacytidine-induced MSCs do not produce this effect. An in vivo study by Kidd et al found that the FAP+ and FSP+ TAF cells in tumor tissues were mainly derived from bone marrow MSCs, whereas vascular endothelial cells in tumor tissues were largely derived from nearby adipose tissues [26]. Lin et al found that in certain colon cancer patients, MSCs isolated from tumor tissues exhibited the same chromosomal abnormalities that were present in the colon cancer cells, while in the remaining patients, the tumor cells exhibited chromosomal

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Conclusion