Double-edged sword of mesenchymal stem cells: Cancer-promoting versus therapeutic potential

Abstract

Mesenchymal stem cells (MSCs) derived from adipose tissue, bone marrow, cord blood, and other tissues, have recently attracted much attention as potential therapeutic agents in various diseases because of their trans-differentiation capacity. However, recent studies have suggested that MSCs also appear to contribute to tumor pathogenesis by supporting tumor microenvironments, increasing tumor growth, and eliciting antitumor immune responses. Although some studies suggest that MSCs have inhibitory effects on tumor development, they are overwhelmed by a number of studies showing that MSCs exert stimulatory effects on tumor pathogenesis. In the present review, we summarize a number of findings to provide current information about the therapeutic potential of MSCs in various diseases. We then discuss the potential roles of MSCs in tumor progression.

Keywords: Immune response; mesenchymal stem cells; metastasis; regeneration; tumor progression.

Figure 1

Activation of various oncogenic proteins in mesenchymal stem cells (MSCs) can induce malignant transformation. (a) Introduction of various oncogenic proteins (FLI‐1/EWS, FUS/CHOP, and synovial sarcoma translocated protein [SYT‐SSX1]) into MSCs may cause transformation of these cells into malignant sarcoma cells. (b) C‐X‐C motif chemokine receptor 6 (CXCR6) signaling pathway stimulates the transformation of MSCs into cancer‐associated fibroblasts. (c) Cell fusion between MSCs and gastric mucosal cells under Helicobacter pylori infection increases the risk of developing gastric carcinoma.

Figure 2

Various factors are responsible for mesenchymal stem cells (MSCs) tropism towards tumor sites. Various factors, such as basic fibroblast growth factor (bFGF), hepatoma‐derived growth factor (HDGF), interleukin 6 (IL‐6), monocyte chemoattractant protein‐1 (MCP‐1), stromal cell‐derived factor 1 (SDF‐1), urokinase‐type plasminogen activator (uPA), and vascular endothelial growth factor (VEGF), have been involved in the migration capacity of MSCs toward tumor xenografts.

Figure 3

Schematic diagram summarizing the potential roles of mesenchymal stem cells (MSCs) in tumor development. Although some studies suggest that MSCs have inhibitory effects on cancer cell growth and metastasis, they are overwhelmingly outnumbered by a number of studies showing that MSCs have the ability to migrate into tumor sites and exert stimulatory effects on tumor development by secreting a number of paracrine factors, such as chemokines, cytokines, growth factors, and immune modulatory factors. CXCL, chemokine (C‐X‐C motif) ligand; EGF, epidermal growth factor; IGF‐1, insulin‐like growth factor; IL, interleukin; KGF, keratinocyte growth factor; NK, killer cell; VEGF, vascular endothelial growth factor.