title: Dexamethasone inhibits in vivo tumor growth by the alteration of bone marrow CD11b⁺ myeloid cells.
abstract: Inflammation is closely associated with tumor growth, which is mediated by the activation of bone marrow-derived CD11b(+) cells. Here, we investigated whether anti-inflammatory dexamethasone (Dex), a synthetic glucocorticoid (GC), could regulate tumor growth and CD11b(+) myeloid bone marrow cells (BMCs) in lymphocyte (R1), monocyte (R2) and granulocyte (R3) regions of FSC-SSC dot plot. The growth of B16F10 mouse melanoma tumor was inhibited in Dex-injected group. Lung metastasis was decreased and the lifespan was elongated in Dex-injected mice with tumor resection. Intravenous injection of B16F10 cells increased the percentage of CD11b(+) myeloid BMCs in R1 and R2 regions from 3h to 72h. In contrast, little changes in the percentage of CD11b(+) myeloid BMCs were detected in R3 region. Among CD11b(+) myeloid BMCs, the percentage of CD11b(+)Gr-1(+) cells was increased in R1, R2 and R3 regions. Absolute number of CD11b(+) and CD11b(+)Gr-1(+) cells was enhanced in R1 region from 3h to 72 h. B16F10 tumor growth was significantly increased by intravenous injection of CD11b(+) BMCs. Tumor-bearing mice showed an increase in the percentage of CD11b(+) myeloid BMCs in R2 region and CD11b(+)Gr-1(+) cells in R2 and R3 regions, which are reduced by intravenous injection with Dex. Absolute number of CD11b(+)Gr-1(+) cells was enhanced in R2 and R3 regions. Tumor growth was significantly inhibited by intravenous injection of BMCs collected from Dex-treated tumor-bearing mice. Taken together, data demonstrate that tumor regression by Dex was resulted from the alteration of CD11b(+) myeloid BMCs and their inhibitory function to tumor growth. It suggests that CD11b(+) myeloid BMCs could regulate antitumor efficacy of GCs such as Dex.
authors: Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Republic of Korea. Electronic address: eunyimoon@sejong.ac.kr.
authors: Eun-Yi
authors: EY
authors: Moon
authors: Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Republic of Korea.
authors: Yun-Kyoung
authors: YK
authors: Ryu
authors: Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Republic of Korea.
authors: Geun-Hee
authors: GH
authors: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008546:Melanoma, Experimental / Q000178:diet therapy / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D022423:Myeloid Cells / Q000187:drug effects* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D003907:Dexamethasone
keywords: Bone marrow cells; CD11b(+); CD11b(+)Gr-1(+); Dexamethasone; MDSC; Tumor growth