Close Interactions between Mesenchymal Stem Cells and Neuroblastoma Cell Lines Lead to Tumor Growth Inhibition
Open Access
- 31 October 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (10), e48654
- https://doi.org/10.1371/journal.pone.0048654
Abstract
Mesenchymal stem cells (MSCs) have attracted much interest in oncology since they exhibit marked tropism for the tumor microenvironment and support or suppress malignant cell growth depending on the tumor model tested. The aim of this study was to investigate the role of MSCs in the control of the growth of neuroblastoma (NB), which is the second most common solid tumor in children. In vivo experiments showed that systemically administered MSCs, under our experimental conditions, did not home to tumor sites and did not affect tumor growth or survival. However, MSCs injected intratumorally in an established subcutaneous NB model reduced tumor growth through inhibition of proliferation and induction of apoptosis of NB cells and prolonged the survival of hMSC-treated mice. The need for contact between MSCs and NB cells was further supported by in vitro experiments. In particular, MSCs were found to be attracted by NB cells, and to affect NB cell proliferation with different results depending on the cell line tested. Moreover, NB cells, after pre-incubation with hMSCs, acquired a more invasive behavior towards CXCL12 and the bone marrow, i.e., the primary site of NB metastases. In conclusion, this study demonstrates that functional cross-talk between MSCs and NB cell lines used in our experiments can occur only within short range interaction. Thus, this report does not support the clinical use of MSCs as vehicles for selective delivery of antitumor drugs at the NB site unless chemotherapy and/or radiotherapy create suitable local conditions for MSCs recruitment.Keywords
This publication has 65 references indexed in Scilit:
- Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6Cell Stem Cell, 2009
- Concentration-dependent inhibition of angiogenesis by mesenchymal stem cellsBlood, 2009
- Mesenchymal Stem Cell Transition to Tumor-Associated Fibroblasts Contributes to Fibrovascular Network Expansion and Tumor ProgressionPLOS ONE, 2009
- Reconstitution of Schwannian Stroma in Neuroblastomas Using Human Bone Marrow Stromal CellsThe American Journal of Pathology, 2008
- Mesenchymal stem cells in health and diseaseNature Reviews Immunology, 2008
- Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signallingCancer Letters, 2008
- Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Mediate Human Stem Cell Tropism to Malignant Solid TumorsThe International Journal of Cell Cloning, 2008
- The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro and in vivoCancer Biology & Therapy, 2008
- Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cellsBlood, 2004
- Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animalsBlood, 2003