Adipose Stem Cells and Their Interplay with Cancer Cells and Mitochondrial Reservoir: A New Promising Target

Abstract

Adipose-derived stem cells (ASCs) significantly influence tumor progression within the tumor microenvironment (TME). This review examines the pro-tumorigenic roles of ASCs, focusing on paracrine signaling, direct cell-cell interactions, and immunomodulation. ASC-mediated mitochondrial transfer through tunneling nanotubes (TNTs) and gap junctions (GJs) plays a significant role in enhancing cancer cell survival and metabolism. Cancer cells with dysfunctional mitochondria acquire mitochondria from ASCs to meet their metabolic needs and thrive in the TME. Targeting mitochondrial transfer, modulating ASC function, and influencing metabolic pathways are potential therapeutic strategies. However, challenges like TME complexity, specificity, safety concerns, and resistance mechanisms must be addressed. Disrupting the ASC-cancer cell-mitochondria axis offers a promising approach to cancer therapy.

Keywords: ASCs; CSCs; TME; cancer therapy; drug resistance; mitochondria.

Figure 1

General characteristics of adipose-derived stem cells (ASCs) and their influence in the tumor microenvironment (TME) (Created by Biorender.com).

Figure 2

Mechanisms of mitochondrial transfer. (A) Tunneling nanotubes (TNTs): TNTs are nanoscale membranous channels between cells, with diameters ranging from 50 to 1500 nm, lengths of 5–200 μm, and thicknesses up to 700 nm. (B) Gap junctions (GJs): GJs are made from the head-to-head docking of hexameric assemblies (connexons) of tetraspan integral membrane proteins (connexins (Cx)). (C) Extracellular vesicles (EVs): EVs are nanosized bilayer vesicles secreted by cells and are of three types: microvesicles (MVs), exosomes, and apoptotic bodies. (Created using Biorender.com).