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Review
. 2022 Aug 25;40(8):705-715.
doi: 10.1093/stmcls/sxac036.

Carcinoma-Associated Mesenchymal Stem/Stromal Cells: Architects of the Pro-tumorigenic Tumor Microenvironment

Len Frisbie  1 , Ronald J Buckanovich  2   3 , Lan Coffman  2   3
Affiliations
Review

Carcinoma-Associated Mesenchymal Stem/Stromal Cells: Architects of the Pro-tumorigenic Tumor Microenvironment

Len Frisbie et al. Stem Cells. .

Abstract

The interaction between tumor cells and non-malignant hosts cells within the tumor microenvironment (TME) is critical to the pathophysiology of cancer. These non-malignant host cells, consisting of a variety of stromal, immune, and endothelial cells, engage in a complex bidirectional crosstalk with the malignant tumor cells. Mesenchymal stem/stromal cells (MSCs) are one of these host cells, and they play a critical role in directing the formation and function of the entire TME. These MSCs are epigenetically reprogrammed by cancer cells to assume a strongly pro-tumorigenic phenotype and are referred to as carcinoma-associated mesenchymal stem/stromal cells (CA-MSCs). Studies over the last decade demonstrate that CA-MSCs not only directly interact with cancer cells to promote tumor growth and metastasis but also orchestrate the formation of the TME. Carcinoma-associated mesenchymal stem/stromal cells can differentiate into virtually all stromal sub-lineages present in the TME, including pro-tumorigenic cancer-associated fibroblasts (CAF), myofibroblasts, and adipocytes. carcinoma-associated mesenchymal stem/stromal cells and the CAFs they produce, secrete much of the extracellular matrix in the TME. Furthermore, CA-MSC secreted factors promote angiogenesis, and recruit immunosuppressive myeloid cells effectively driving tumor immune exclusion. Thus CA-MSCs impact nearly every aspect of the TME. Despite their influence on cancer biology, as CA-MSCs represent a heterogenous population without a single definitive marker, significant confusion remains regarding the origin and proper identification CA-MSCs. This review will focus on the impact of CA-MSCs on cancer progression and metastasis and the ongoing work on CA-MSC identification, nomenclature and mechanism of action.

Keywords: mesenchymal stem cell; metastatic niche; stroma; tumor microenvironment.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Mesenchymal stem/stromal cells (MSCs) can differentiate into several lineages which make up the stromal tumor microenvironment (TME).
Figure 2.
Figure 2.
Carcinoma-associated mesenchymal stem cells (CA-MSCs) are reprogrammed from naïve MSCs and have several tumor supporting functions.
Figure 3.
Figure 3.
CA-MSCs function within and form the mature TME through differentiation and direct interaction.
See this image and copyright information in PMC

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