The Role of Amino Acids in the Crosstalk Between Mesenchymal Stromal Cells and Neoplastic Cells in the Hematopoietic Niche.

Martina Chiu,Ovidio Bussolati,Giuseppe Taurino,Massimiliano G Bianchi

doi:10.3389/fcell.2021.714755

Martina Chiu, Ovidio Bussolati + Show 2 more

Open Access

https://doi.org/10.3389/fcell.2021.714755

Copy DOI

Abstract

Within the bone marrow hematopoietic cells are in close connection with mesenchymal stromal cells (MSCs), which influence the behavior and differentiation of normal or malignant lymphoid and myeloid cells. Altered cell metabolism is a hallmark of cancer, and changes in nutrient pools and fluxes are important components of the bidirectional communication between MSCs and hematological cancer cells. Among nutrients, amino acids play a significant role in cancer progression and chemo-resistance. Moreover, selected types of cancer cells are extremely greedy for glutamine, and significantly deplete the extracellular pool of the amino acid. As a consequence, this influences the behavior of MSCs in terms of either cytokine/chemokine secretion or differentiation potential. Additionally, a direct nutritional interaction exists between MSCs and immune cells. In particular, selected subpopulations of lymphocytes are dependent upon selected amino acids, such as arginine and tryptophan, for full differentiation and competence. This review describes and discusses the nutritional interactions existing in the neoplastic bone marrow niche between MSCs and other cell types, with a particular emphasis on cancer cells and immune cells. These relationships are discussed in the perspective of potential novel therapeutic strategies based on the interference on amino acid metabolism or intercellular fluxes.

Highlights

Mesenchymal stromal cells (MSCs) are pluripotent stem cells able to differentiate into osteoblasts, chondroblasts and adipocytes
In the case of myeloma, besides being an Achille’s heel potentially targetable in clinics, the huge consumption of Gln by cancer cells causes a partial depletion of the amino acid in the bone marrow (BM), where Gln concentration decreases in vivo from 0.6 to 0.4 mM (Bolzoni et al, 2016)
In this review we recapitulated the involvement of some amino acids in the complex cross-talks existing among hematological cancer cells and MSCs within the BM context (Figure 1)

Summary

INTRODUCTION

Mesenchymal stromal cells (MSCs) are pluripotent stem cells able to differentiate into osteoblasts, chondroblasts and adipocytes. A nutritional interaction and, possibly, a competition exist between cancer cells, MSCs and other cells of the BM niche. In this context, amino acids play a significant role in cancer progression and chemoresistance (Vettore et al, 2020). Cancer cells are extremely avid for a particular amino acid, so that the extracellular compartment is significantly depleted, influencing the behavior of MSCs in terms of either cytokine/chemokine secretion or differentiation ability. A direct nutritional interaction exists between MSCs and several types of immunity cells, which are themselves dependent upon selected amino acids for differentiation and activity. The secreted citrulline is taken up by T-ALL blasts, which, subsequently, convert it into argininosuccinate and, eventually, into Arg trough the activity of Argininosuccinate Synthetase (ASS) and Argininosuccinate Lyase (ASL) (Sugimura et al, 1990)

ASPARAGINE AND ASPARTATE

Findings

CONCLUSION