Malignant astrocytic tumor progression potentiated by JAK-mediated recruitment of myeloid cells Journal Article
| Authors: | Rajappa, P.; Cobb, W. S.; Vartanian, E.; Huang, Y.; Daly, L.; Hoffman, C.; Zhang, J.; Shen, B.; Yanowitch, R.; Garg, K.; Cisse, B.; Haddock, S.; Huse, J.; Pisapia, D. J.; Chan, T. A.; Lyden, D. C.; Bromberg, J. F.; Greenfield, J. P. |
| Article Title: | Malignant astrocytic tumor progression potentiated by JAK-mediated recruitment of myeloid cells |
| Abstract: | Purpose: While the tumor microenvironment has been known to play an integral role in tumor progression, the function of nonresident bone marrow-derived cells (BMDC) remains to be determined in neurologic tumors. Here we identified the contribution of BMDC recruitment in mediating malignant transformation from low- to high-grade gliomas. Experimental Design: We analyzed human blood and tumor samples from patients with low- and high-grade gliomas. A spontaneous platelet-derived growth factor (PDGF) murine glioma model (RCAS) was utilized to recapitulate human disease progression. Levels of CD11b+/GR1+ BMDCs were analyzed at discrete stages of tumor progression. Using bone marrow transplantation, we determined the unique influence of BMDCs in the transition from low- to high-grade glioma. The functional role of these BMDCs was then examined using a JAK 1/2 inhibitor (AZD1480). Results: CD11b+ myeloid cells were significantly increased during tumor progression in peripheral blood and tumors of glioma patients. Increases in CD11b+/GR1+ cells were observed in murine peripheral blood, bone marrow, and tumors during low-grade to high-grade transformation. Transient blockade of CD11b+ cell expansion using a JAK 1/2 Inhibitor (AZD1480) impaired mobilization of these cells and was associated with a reduction in tumor volume, maintenance of a low-grade tumor phenotype, and prolongation in survival. Conclusions: We demonstrate that impaired recruitment of CD11b+ myeloid cells with a JAK1/2 inhibitor inhibits glioma progression in vivo and prolongs survival in a murine glioma model. ©2016 AACR. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 23 |
| Issue: | 12 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2017-06-15 |
| Start Page: | 3109 |
| End Page: | 3119 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-16-1508 |
| PROVIDER: | scopus |
| PUBMED: | 28039266 |
| PMCID: | PMC5769921 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2017 -- Source: Scopus |
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