CXCR4-Expressing Glial Precursor Cells Demonstrate Enhanced Migratory Tropism for Glioma

Moneeb Ehtesham, Reid C. Thompson

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, USA..

DOI: 10.4236/jct.2012.36142                

Abstract

Malignant glioma remains one of the most intractable of human cancers principally due to the highly infiltrative nature of these neoplasms. The use of neural precursor cells (NPC) has received considerable attention based on their ability to selectively migrate towards disseminated areas of tumor in vivo and their described ability to deliver tumor-directed therapies specifically to infiltrating tumor cells. Fundamental to optimizing the use of these cells for potential clinical translation is the development of an understanding regarding the biologic cues that govern their ability to migrate towards infiltrative glioma foci. To this end, in this paper we detail that NPC selected for double-expression of the glial-precursor marker A2B5 and the cell-surface chemokine receptor, CXCR4, demonstrate enhanced in vitro gliomadirected tropism. These findings demonstrate the relevance of these markers for the phenotypic segregation of an optimally tumor-tropic NPC sub-population as a means of enhancing NPC-based therapeutic strategies for the treatment of glioma.

Keywords

Glioma; CXCR4; Neural Precursor Cells; Brain Tumor(s)

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	T. S. Surawicz, F. Davis, S. Freels, E. R. Laws Jr. and H. R. Menck, “Brain Tumor Survival: Results from the National Cancer Data Base,” Journal of Neuro-Oncology, Vol. 40, No. 2, 1998, pp. 151-160. doi:10.1023/A:1006091608586
[2]	K. S. Aboody, A. Brown, N. G. Rainov, et al., “Neural Stem Cells Display Extensive Tropism for Pathology in Adult Brain: Evidence from Intracranial Gliomas,” Proceedings of the National Academy of Sciences, Vol. 97, 2000, pp. 12846-12851. doi:10.1073/pnas.97.23.12846
[3]	S. Benedetti, B. Pirola, B. Pollo, et al., “Gene Therapy of Experimental Brain Tumors Using Neural Progenitor Cells,” Nature Medicine, Vol. 6, 2000, pp. 447-450. doi:10.1038/74710
[4]	M. Ehtesham, P. Kabos, K. L. Black and J. S. Yu, “Use of Neural Stem Cells as Therapeutic Vehicles for the Treatment of Malignant Glioma,” Expert Review of Neurotherapeutics, Vol. 3, No. 6, 2003, pp. 883-895. doi:10.1586/14737175.3.6.883
[5]	M. Ehtesham, P. Kabos, M. A. Gutierrez, et al., “Induction of Glioblastoma Apoptosis Using Neural Stem Cell-Mediated Delivery of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand,” Cancer Research, Vol. 62, No. 24, 2002, pp. 7170-7174.
[6]	M. Ehtesham, P. Kabos, A. Kabosova, T. Neuman, K. L. Black and J. S. Yu, “The Use of Interleukin 12-Secreting Neural Stem Cells for the Treatment of Intracranial Glioma,” Cancer Research, Vol. 62, No. 20, 2002, pp. 5657-5663.
[7]	U. Herrlinger, C. Woiciechowski, M. Sena-Esteves, et al., “Neural Precursor Cells for Delivery of Replication-Conditional HSV-1 Vectors to Intracerebral Gliomas,” Molecular Therapy, Vol. 1, No. 4, 2000, pp. 347-357. doi:10.1006/mthe.2000.0046
[8]	K. Y. Mapara, C. B. Stevenson, R. C. Thompson and M. Ehtesham, “Stem Cells as Vehicles for the Treatment of Brain Cancer,” Neurosurgery Clinics of North America, Vol. 18, No. 1, 2007, pp. 71-80. doi:10.1016/j.nec.2006.10.001
[9]	M. Ehtesham, X. Yuan, P. Kabos, et al., “Glioma Tropic Neural Stem Cells Consist of Astrocytic Precursors and Their Migratory Capacity Is Mediated by CXCR4,” Neo-plasia, Vol. 6, No. 3, 2004, pp. 287-293. doi:10.1593/neo.03427
[10]	F. Lazarini, T. N. Tham, P. Casanova, F. Arenzana-Seisdedos and M. Dubois-Dalcq, “Role of the Alpha-Chemokine Stromal Cell-Derived Factor (SDF-1) in the Developing and Mature Central Nervous System,” Glia, Vol. 42, No. 2, 2003, pp. 139-148. doi:10.1002/glia.10139
[11]	K. Reiss, R. Mentlein, J. Sievers and D. Hartmann, “Stromal Cell-Derived Factor 1 Is Secreted by Meningeal Cells and Acts as Chemotactic Factor on Neuronal Stem Cells of the Cerebellar External Granular Layer,” Neuroscience, Vol. 115, No. 1, 2002, pp. 295-305. doi:10.1016/S0306-4522(02)00307-X
[12]	S. Barbero, R. Bonavia, A. Bajetto, et al., “Stromal Cell-Derived Factor 1alpha Stimulates Human Glioblastoma Cell Growth through the Activation of Both Extracellular Signal-Regulated Kinases 1/2 and Akt,” Cancer Research, Vol. 63, No. 8, 2003, pp. 1969-1974.
[13]	M. Ehtesham, J. A. Winston, P. Kabos and R. C. Thompson, “CXCR4 Expression Mediates Glioma Cell Invasiveness,” Oncogene, Vol. 25, No. 19, 2006, pp. 2801-2806. doi:10.1038/sj.onc.1209302
[14]	S. A. Rempel, S. Dudas, S. Ge and J. A. Gutierrez, “Identification and Localization of the Cytokine SDF1 and Its Receptor, CXC Chemokine Receptor 4, to Regions of Necrosis and Angiogenesis in Human Glioblastoma,” Clinical Cancer Research, Vol. 6, No. 1, 2000, pp. 102-111.
[15]	P. Rajan and R. D. McKay, “Multiple Routes to Astrocytic Differentiation in the CNS,” Journal of Neuroscience, Vol. 18, No. 10, 1998, pp. 3620-3629.
[16]	M. C. Nunes, N. S. Roy, H. M. Keyoung, et al., “Identification and Isolation of Multipotential Neural Progenitor Cells from the Subcortical White Matter of the Adult Human Brain,” Nature Medicine, Vol. 9, 2003, pp. 439-447. doi:10.1038/nm837
[17]	M. Ehtesham, C. B. Stevenson and R. C. Thompson, “Stem Cell Therapies for Malignant Glioma,” Neurosurgical Focus, Vol. 19, No. 3, 2005, p. E5. doi:10.3171/foc.2005.19.3.6