Intercellular Communication in Tumor Biology: A Role for Mitochondrial Transfer.

Patries M Herst,Michael V Berridge,Rebecca H Dawson

doi:10.3389/fonc.2018.00344

Abstract

Intercellular communication between cancer cells and other cells in the tumor microenvironment plays a defining role in tumor development. Tumors contain infiltrates of stromal cells and immune cells that can either promote or inhibit tumor growth, depending on the cytokine/chemokine milieu of the tumor microenvironment and their effect on cell activation status. Recent research has shown that stromal cells can also affect tumor growth through the donation of mitochondria to respiration-deficient tumor cells, restoring normal respiration. Nuclear and mitochondrial DNA mutations affecting mitochondrial respiration lead to some level of respiratory incompetence, forcing cells to generate more energy by glycolysis. Highly glycolytic cancer cells tend to be very aggressive and invasive with poor patient prognosis. However, purely glycolytic cancer cells devoid of mitochondrial DNA cannot form tumors unless they acquire mitochondrial DNA from adjacent cells. This perspective article will address this apparent conundrum of highly glycolytic cells and cover aspects of intercellular communication between tumor cells and cells of the microenvironment with particular emphasis on intercellular mitochondrial transfer.

Highlights

Tumor development depends critically on the intimate interplay between individual neoplastic cells, normal cells from the tissue of origin, and their abiotic environment
The primary donor cell types used in co-cultures to investigate mitochondrial transfer to cancer cells have been bone marrowderived mesenchymal stem or stromal cells (BM-MESENCHYMAL ORIGIN (MSC)), MSCs can be derived from many different tissues
The first demonstration of mitochondrial transfer to tumor cells involved co-culture of human A549 lung adenocarcinoma cells without mtDNA (ρ◦ cells) with human Bone marrow (BM)-MSCs [38]. This seminal study showed that auxotrophy for uridine and pyruvate was lost and respiration restored in clones that had acquired mtDNA, and that the mitochondrial genotype was that of the donor BM-MSCs

Summary

Introduction

Tumor development depends critically on the intimate interplay between individual neoplastic cells, normal cells from the tissue of origin, and their abiotic environment. Cells with mutated mtDNA or decreased mtDNA copy number have reduced ability to use the electron transport chain and may rely on glycolytic energy production, but they are still able to synthesize pyrimidines and are able to form tumors in vivo.

Results

Conclusion