Data from Malignant Astrocytic Tumor Progression Potentiated by JAK-mediated Recruitment of Myeloid Cells

التفاصيل البيبلوغرافية
العنوان: Data from Malignant Astrocytic Tumor Progression Potentiated by JAK-mediated Recruitment of Myeloid Cells
المؤلفون: Jeffrey P. Greenfield, Jacqueline F. Bromberg, David C. Lyden, Timothy A. Chan, David J. Pisapia, Jason Huse, Sara Haddock, Babacar Cisse, Kunal Garg, Rachel Yanowitch, Beiyi Shen, Jane Zhang, Caitlin Hoffman, Laura Daly, Yujie Huang, Emma Vartanian, William S. Cobb, Prajwal Rajappa
بيانات النشر: American Association for Cancer Research (AACR), 2023.
سنة النشر: 2023
الوصف: 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. Clin Cancer Res; 23(12); 3109–19. ©2016 AACR.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a810b30b0e12133ab2f34f4ba7d59c4
https://doi.org/10.1158/1078-0432.c.6525029.v1
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....2a810b30b0e12133ab2f34f4ba7d59c4
قاعدة البيانات: OpenAIRE