Differential Impact of Calcitriol and Its Analogs on Tumor Stroma in Young and Aged Ovariectomized Mice Bearing 4T1 Mammary Gland Cancer

被引:11
|
作者
Anisiewicz, Artur [1 ]
Pawlik, Agata [1 ]
Filip-Psurska, Beata [1 ]
Wietrzyk, Joanna [1 ]
机构
[1] Polish Acad Sci, Hirszfeld Inst Immunol & Expt Therapy, Dept Expt Oncol, PL-53114 Wroclaw, Poland
关键词
breast cancer; tumor stroma; metastasis; immunity; elderly; calcitriol; vitamin D; BREAST-CANCER; VITAMIN-D; ANTIPROLIFERATIVE ACTIVITY; 1,25-DIHYDROXYVITAMIN D-3; CARCINOMA; 4T1; TGF-BETA; PROGRESSION; GROWTH; METASTASIS; CELLS;
D O I
10.3390/ijms21176359
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
(1) Background: Vitamin D compounds (VDC) are extensively studied in the field of anticancer properties, including breast cancer. Previously, we showed that calcitriol and its analogs (PRI-2191 and PRI-2205) stimulate metastasis in 4T1 murine mammary gland cancer models in young mice, whereas the reverse effect was observed in aged ovariectomized (OVX) mice; (2) Methods: We determined the phenotype of monocytes/macrophages using FACS and examined the expression of selected genes and proteins by Real-Time PCR and ELISA; (3) Results: Activities of VDC are accompanied by an increase in the percentage of Ly6C(low)anti-inflammatory monocytes in the spleen of young and a decrease in aged OVX mice. Treatment of young mice with VDC resulted in an increase of CCL2 plasma and tumor concentration and Arg1 in tumor. In later stage of tumor progression the expression of genes related to metastasis in lung tissue was decreased or increased, in old OVX or young mice, respectively; (4) Conclusions: Pro- or anti-metastatic effects of calcitriol and its analogs in young or aged OVX mice, respectively, can be attributed to the differences in the effects of VDC on the tumor microenvironment, as a consequence of differences in the immunity status of young and aged mice.
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页码:1 / 24
页数:24
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