Mesenchymal Stem Cells Contribute to Tumor Cell Proliferation by Direct Cell-Cell Contact Interactions

ABSTRACT

Bone marrow (BM)-derived mesenchymal stem cells (MSCs) have been implicated in tumor progression, making MSCs important targets for anti-cancer strategies. In this study, we show that MSCs promote tumor growth in vivo in a lymphoma xenograft model. We show that MSCs provide direct cell–cell contact interactions and, to a lesser extend, soluble factors that promote tumor cell proliferation and survival in vitro. PTK787/ZK 222584 reduces tumor growth-promoting effects of MSCs both in vitro and in vivo. Our results address the importance of targeting the MSCs for future anti-cancer strategies.

Keywords: :

• Mesenchymal stem cells
• Tumor growth
• Angiogenesis
• Vessel density
• Proliferation
• Apoptosis
• PTK787/ZK 222584

ACKNOWLEDGMENTS

Berber D. Roorda is supported by Stichting KIKA (Kinderen Kankervrij), the Netherlands. Eveline S. J. M. de Bont is supported by a grant of the Dutch Cancer Society (grant no. 3661). Furthermore, we would like to thank all surgeons from the department of Thorax Surgery, UMCG, the Netherlands, for their cooperation in obtaining bone marrow aspirates.

Declaration of Interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.