Tropism of mesenchymal stem cell toward CD133+ stem cell of glioblastoma in vitro and promote tumor proliferation in vivo

Abstract

BackgroundPrevious studies have demonstrated remarkable tropism of mesenchymal stem cells (MSCs) toward malignant gliomas, making these cells a potential vehicle for delivery of therapeutic agents to disseminated glioblastoma (GBM) cells. However, the potential contribution of MSCs to tumor progression is a matter of concern. It has been suggested that CD133+ GBM stem cells secrete a variety of chemokines, including monocytes chemoattractant protein-1 (MCP-1/CCL2) and stromal cell-derived factor-1(SDF-1/CXCL12), which could act in this tropism. However, the role in the modulation of this tropism of the subpopulation of CD133+ cells, which initiate GBM and the mechanisms underlying the tropism of MSCs to CD133+ GBM cells and their effects on tumor development, remains poorly defined.Methods/resultsWe found that isolated and cultured MSCs (human umbilical cord blood MSCs) express CCR2 and CXCR4, the respective receptors for MCP-1/CCL2 and SDF-1/CXCL12, and demonstrated, in vitro, that MCP-1/CCL2 and SDF-1/CXC12, secreted by CD133+ GBM cells from primary cell cultures, induce the migration of MSCs. In addition, we confirmed that after in vivo GBM tumor establishment, by stereotaxic implantation of the CD133+ GBM cells labeled with Qdots (705 nm), MSCs labeled with multimodal iron oxide nanoparticles (MION) conjugated to rhodamine-B (Rh-B) (MION-Rh), infused by caudal vein, were able to cross the blood-brain barrier of the animal and migrate to the tumor region. Evaluation GBM tumors histology showed that groups that received MSC demonstrated tumor development, glial invasiveness, and detection of a high number of cycling cells.ConclusionsTherefore, in this study, we validated the chemotactic effect of MCP-1/CCL2 and SDF-1/CXCL12 in mediating the migration of MSCs toward CD133+ GBM cells. However, we observed that, after infiltrating the tumor, MSCs promote tumor growth in vivo probably by release of exosomes. Thus, the use of these cells as a therapeutic carrier strategy to target GBM cells must be approached with caution.

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

“…Finally, glioma CSCs have been shown to secrete stromal cell-derived factor 1 (SDF-1/CXCL12) in order to recruit MSCs [60]. MSCs also secrete SDF-1/CXCL12, and communication between CSCs and MSCs through SDF-1/CXCL12 leads to tumor progression through different ways, including CSs survival, tumor growth, metastasis and angiogenesis processes [61,62].…”

Crosstalk Between Mesenchymal Stromal Cells and Tumor-Associated Macrophages in Gastric Cancer

“…Due to their tumor tropism and immunosuppressive properties, MSCs have been proved to exhibit diverse biological functions in tumor ( 20 ). Numerous studies have provided the evidence that tumor-derived MSCs could promote the growth and metastasis of a variety of malignances, via the secretion of trophic factors or cell-to-cell contact with the other TME cells ( 21 , 22 ).…”

mTOR Modulates Intercellular Signals for Enlargement and Infiltration in Glioblastoma Multiforme

“…Recent intriguing reports implicate MSC-derived exosomes in GBM maintenance. In fact, MSCs represent a newly identified source of growth factors and morphogens that increase GSCs self-renewal, while contributing to tumor growth and tropism [133]. For instance, MSCs release interleukin-6 (IL-6) which can induce pro-tumorigenic effects on GBM by increasing GSC stemness, proliferation and clonogenicity [131].…”