Role of MSC in the Tumor Microenvironment.

Ralf Hass

doi:10.3390/cancers12082107

Abstract

The tumor microenvironment represents a dynamically composed matrix in which tissue-associated cancer cells are embedded together with a variety of further cell types to form a more or less separate organ-like structure. Constantly mutual interactions between cells of the tumor microenvironment promote continuous restructuring and growth in the tumor. A distinct organization of the tumor stroma also facilitates the formation of transient cancer stem cell niches, thereby contributing to progressive and dynamic tumor development. An important but heterogeneous mixture of cells that communicates among the cancer cells and the different tumor-associated cell types is represented by mesenchymal stroma-/stem-like cells (MSC). Following recruitment to tumor sites, MSC can change their functionalities, adapt to the tumor’s metabolism, undergo differentiation and synergize with cancer cells. Vice versa, cancer cells can alter therapeutic sensitivities and change metastatic behavior depending on the type and intensity of this MSC crosstalk. Thus, close cellular interactions between MSC and cancer cells can eventually promote cell fusion by forming new cancer hybrid cells. Consequently, newly acquired cancer cell functions or new hybrid cancer populations enlarge the plasticity of the tumor and counteract successful interventional strategies. The present review article highlights some important features of MSC within the tumor stroma.

Highlights

Human mesenchymal stroma-/stem-like cells (MSC) represent heterogeneous populations which can be derived e.g., from the tunica adventitia in perivascular regions of various adult organs and tissues such as bone marrow, adipose tissue, peripheral blood or dental pulp, among various others [1,2,3,4]
The attraction of MSC to tumor sites involves an aberrant development of adjacent cell types, including the maturation of carcinoma-associated fibroblasts (CAFs) or development of tumor-associated macrophages (TAMs), which build a fibrovascular network as part of the tumor-specific extracellular matrix (ECM)
Immune cells are present throughout the tumor microenvironment (TME) and include populations from the innate and adaptive immune system largely interacting with tumor tissue-associated MSC, whereby lymphocytes represent the majority of tumor-infiltrating immune cells [71]

Summary

Introduction

Human mesenchymal stroma-/stem-like cells (MSC) represent heterogeneous populations which can be derived e.g., from the tunica adventitia in perivascular regions of various adult organs and tissues such as bone marrow, adipose tissue, peripheral blood or dental pulp, among various others [1,2,3,4]. According to further nomenclature for MSC-like multipotent mesenchymal stromal cells or medicinal signaling cells, several cellular functions are associated with these cells, some of which are controversially discussed [5] These include distinct repair activity for damaged tissues [6], involvement in regenerative processes [7], immune-modulatory potential [8], neovascularization [9], paracrine activities, antimicrobial functions [10], and tumor-inhibitory [11] and tumor-promoting properties [12,13,14]. Some immune cell functions can adapt to the tumorigenic environment, such as the conversion of monocytes/macrophages to so-called tumor-associated macrophages (TAMs) Due to their regenerative potential, MSC are recruited to cancer cell-induced lesions to promote tissue repair. The attraction of MSC to tumor sites involves an aberrant development of adjacent cell types, including the maturation of CAFs or development of TAMs, which build a fibrovascular network as part of the tumor-specific ECM

Tumor Stroma

Tumor Organ and Vascularization

MSC and Immune Cell Function in the TME

MSC and Cancer Cell Interactions—Cancer Stem Cell Niche

Conclusions