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Article ; Online: Calcitriol and Its Analogs Establish the Immunosuppressive Microenvironment That Drives Metastasis in 4T1 Mouse Mammary Gland Cancer.

Pawlik, Agata / Anisiewicz, Artur / Filip-Psurska, Beata / Nowak, Marcin / Turlej, Eliza / Trynda, Justyna / Banach, Joanna / Gretkierewicz, Paweł / Wietrzyk, Joanna

International journal of molecular sciences

2018  Volume 19, Issue 7

Abstract: In our previous study, calcitriol and its analogs PRI-2191 and PRI-2205 stimulated 4T1 mouse mammary gland cancer metastasis. Therefore, we aimed to analyze the inflammatory response in 4T1-bearing mice treated with these compounds. Gene expression ... ...

Abstract In our previous study, calcitriol and its analogs PRI-2191 and PRI-2205 stimulated 4T1 mouse mammary gland cancer metastasis. Therefore, we aimed to analyze the inflammatory response in 4T1-bearing mice treated with these compounds. Gene expression analysis of the splenocytes and regional lymph nodes demonstrated prevalence of the T helper lymphocytes (Th2) response with an increased activity of regulatory T (Treg) lymphocytes in mice treated with these compounds. We also observed an increased number of mature granulocytes and B lymphocytes and a decreased number of TCD4⁺, TCD4⁺CD25⁺, and TCD8⁺, as well as natural killer (NK) CD335⁺, cells in the blood of mice treated with calcitriol and its analogs. Among the splenocytes, we observed a significant decrease in NK CD335⁺ cells and an increase in TCD8⁺ cells. Calcitriol and its analogs decreased the levels of interleukin (IL)-1β and IL-10 and increased the level of interferon gamma (IFN-γ) in the plasma. In the tumor tissue, they caused an increase in the level of IL-10. Gene expression analysis of lung tissue demonstrated an increased level of osteopontin (
MeSH term(s) Animals ; B-Lymphocytes/drug effects ; B-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/metabolism ; Calcitriol/analogs & derivatives ; Calcitriol/pharmacology ; Cells, Cultured ; Dihydroxycholecalciferols/pharmacology ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Granulocytes/drug effects ; Granulocytes/metabolism ; Immunosuppressive Agents/pharmacology ; Mammary Neoplasms, Experimental/metabolism ; Mammary Neoplasms, Experimental/pathology ; Mice ; Mice, Inbred BALB C ; Osteopontin/genetics ; Real-Time Polymerase Chain Reaction ; Transforming Growth Factor beta/genetics
Chemical Substances Dihydroxycholecalciferols ; Immunosuppressive Agents ; Transforming Growth Factor beta ; Osteopontin (106441-73-0) ; calcipotriene (143NQ3779B) ; 1 alpha,24-dihydroxyvitamin D3 (60965-80-2) ; Calcitriol (FXC9231JVH)
Language English
Publishing date 2018-07-20
Publishing country Switzerland
Document type Journal Article
ZDB-ID 2019364-6
ISSN 1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online) 1422-0067
ISSN 1422-0067 ; 1661-6596
DOI 10.3390/ijms19072116
Database MEDical Literature Analysis and Retrieval System OnLINE

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