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


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)-1? and IL-10 and increased the level of interferon gamma (IFN-?) 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 (Spp1) and transforming growth factor ? (TGF-?) mRNA. The expression of Spp1 was also elevated in lymph nodes. Calcitriol and its analogs caused prevalence of tumor-conducive changes in the immune system of 4T1 tumor-bearing mice, despite the induction of some tumor-disadvantageous effects.

SUBMITTER: Pawlik A 

PROVIDER: S-EPMC6073894 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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

Pawlik Agata A   Anisiewicz Artur A   Filip-Psurska Beata B   Nowak Marcin M   Turlej Eliza E   Trynda Justyna J   Banach Joanna J   Gretkierewicz Paweł P   Wietrzyk Joanna J  

International journal of molecular sciences 20180720 7


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 n  ...[more]

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