Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma
By A. Khakoo, S. Pati, S. Anderson, William Reid, M. Elshal, I. Rovira, A. T. Nguyen, D. Malide, C. Combs, G. Hall and 7 more. Journal of Experimental Medicine, 2006
775 citations recorded by the source corpus.
Emerging evidence suggests that both human stem cells and mature stromal cells can play an important role in the development and growth of human malignancies. In contrast to these tumor-promoting properties, we observed that in an in vivo model of Kaposi's sarcoma (KS), intravenously (i.v.) injected human mesenchymal stem cells (MSCs) home to sites of tumorigenesis and potently inhibit tumor growth. We further show that human MSCs can inhibit the in vitro activation of the Akt protein kinase within some but not all tumor and primary cell lines. The inhibition of Akt activity requires the MSCs to make direct cell–cell contact and can be inhibited by a neutralizing antibody against E-cadherin. We further demonstrate that in vivo, Akt activation within KS cells is potently down-regulated in areas adjacent to MSC infiltration. Finally, the in vivo tumor-suppressive effects of MSCs correlates with their ability to inhibit target cell Akt activity, and KS tumors engineered to express a constitutively activated Akt construct are no longer sensitive to i.v. MSC administration. These results suggest that in contrast to other stem cells or normal stromal cells, MSCs possess intrinsic antineoplastic properties and that this stem cell population might be of particular utility for treating those human malignancies characterized by dysregulated Akt.
Subfields: Oncology, Pathology and Forensic Medicine, Physiology
View Paper: https://www.semanticscholar.org/paper/ffbb03c1253f97d189454fb8e2379c8a37328dea
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Citations in the corpus
- Ethical and Safety Issues of Stem Cell-Based Therapy (2018, background): “Injected MSCs migrate to the metastatic sites [74] and produce pro-angiogenic factors: vascular endothelial growth factor, basic fibroblast growth factor, TGF-β, platelet-derived growth factor, angiopoietin-1, placental growth factor, IL-6, monocyte chemotactic protein-1, HGF, resulting with neo-vas”
- Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. (2008, result): “This agrees with a recent report showing that naive hMSCs can inhibit tumor growth in vivo in a model of Kaposi’s sarcoma (34).”
- Mesenchymal Stem Cell Transition to Tumor-Associated Fibroblasts Contributes to Fibrovascular Network Expansion and Tumor Progression (2009, background): “MSC represent a relatively well-defined ex vivo cell population with complex and poorly understood biology in vivo [28], [29].”