TY - JOUR
T1 - Tumor regulation of myeloid-derived suppressor cell proliferation and trafficking
AU - Younos, Ibrahim H.
AU - Dafferner, Alicia J.
AU - Gulen, Dumrul
AU - Britton, Holly C.
AU - Talmadge, James E.
N1 - Funding Information:
This research was funded by a grant from the Nebraska Research Initiative (NRI) , “Translation of Biotechnology into the Clinic”.
PY - 2012/7
Y1 - 2012/7
N2 - A stress response can induce myeloid progenitor cell (MPC) proliferation, mobilization, and extramedullary hematopoiesis (EMH) within lymphoid and parenchymal organs. Our studies using in vivo BrdU labeling, Ki-67 IHC staining, and carboxyfluorescein succinimidyl ester (CFSE) adoptive cell transfer revealed that spleens, rather than bone marrow (BM) and peripheral blood (PB), from 4T1 mammary tumor-bearing (TB) mice were the primary site of MPC proliferation. The resultant increase in MPCs was associated with tumor hematopoietic growth factor (GF) transcription, decreased apoptosis, as well as, prolonged survival of splenic MPCs. In naïve mice, i.v. injected CFSE-labeled MDSCs (myeloid-derived suppressor cells) initially accumulated in the lungs, while in TB mice, they rapidly sequestered in the spleen. In contrast, a few of the injected MDSCs and leukocytes arrested, proliferated, or accumulated in the marrow, tumor, or PB of TB mice. However, BrdU labeling revealed a significant demargination of proliferating splenic MPCs into the PB. In tumors, despite high GF transcript levels, we found that a high frequency of MDSCs was apoptotic. In summary, tumor growth and cytokines regulate MPC proliferation, trafficking, accumulation, apoptosis, and survival.
AB - A stress response can induce myeloid progenitor cell (MPC) proliferation, mobilization, and extramedullary hematopoiesis (EMH) within lymphoid and parenchymal organs. Our studies using in vivo BrdU labeling, Ki-67 IHC staining, and carboxyfluorescein succinimidyl ester (CFSE) adoptive cell transfer revealed that spleens, rather than bone marrow (BM) and peripheral blood (PB), from 4T1 mammary tumor-bearing (TB) mice were the primary site of MPC proliferation. The resultant increase in MPCs was associated with tumor hematopoietic growth factor (GF) transcription, decreased apoptosis, as well as, prolonged survival of splenic MPCs. In naïve mice, i.v. injected CFSE-labeled MDSCs (myeloid-derived suppressor cells) initially accumulated in the lungs, while in TB mice, they rapidly sequestered in the spleen. In contrast, a few of the injected MDSCs and leukocytes arrested, proliferated, or accumulated in the marrow, tumor, or PB of TB mice. However, BrdU labeling revealed a significant demargination of proliferating splenic MPCs into the PB. In tumors, despite high GF transcript levels, we found that a high frequency of MDSCs was apoptotic. In summary, tumor growth and cytokines regulate MPC proliferation, trafficking, accumulation, apoptosis, and survival.
KW - G-CSF
KW - MDSC
KW - NOS-2
KW - Proliferation
KW - Trafficking
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U2 - 10.1016/j.intimp.2012.05.002
DO - 10.1016/j.intimp.2012.05.002
M3 - Article
C2 - 22609473
AN - SCOPUS:84861422421
SN - 1567-5769
VL - 13
SP - 245
EP - 256
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 3
ER -