Regulation of tumor-induced myelopoiesis and the associated immune suppressor cells in mice bearing metastatic Lewis lung carcinoma by prostaglandin E2.
The in vitro and in vivo effects of prostaglandin E2 (PGE2) and of its stable analogue, 16,16-dimethyl-PGE2 (dmPGE2), on myelopoiesis and on the myelopoiesis-associated immune suppressor cell activity of mice bearing metastatic variant Lewis lung carcinoma (LLC-C3) tumors are assessed. In vitro studies showed a reduced susceptibility of bone marrow myeloid progenitor cells (CFC) from LLC-C3 tumor bearers versus normal mice to the growth-inhibitory effects of PGE2. When added to cocultures of bone marrow cells with LLC-C3 supernatants, PGE2 lessened the frequency of CFC and slightly reduced the generation of bone marrow immune suppressor cells. In vivo studies showed that 4 daily injections of dmPGE2 into LLC-C3 tumor-bearing mice caused some reduction in femoral bone marrow CFC and had an insignificant effect on bone marrow suppressor cell activity. In contrast to the relative insensitivity of bone marrow cells of tumor bearers to the effects of PGE2, in vitro studies showed that CFC formation by spleen cells of tumor bearers was readily inhibited by PGE2. Likewise, in vivo studies showed that spleen cells of dmPGE2-treated LLC-C3-bearing mice had a reduction in cellularity, CFC, and the level of spontaneous proliferation; a reduction in suppressor cell activity; and an increase in blastogenesis. Thus, short-term dmPGE2 treatment of LLC-C3-bearing mice limited the tumor-induced splenic myelopoiesis and reduced the associated splenic immune suppressor cell activity.
Young
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MR
Department of Research Services, Edward J. Hines, Jr., Veterans Administration Hospital, Hines, Illinois 60141.
Young
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ME
Kim
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D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000503:physiopathology*; D013154:Spleen / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2