Abstract
(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 Ly6Clow 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.
Highlights
Numerous studies conducted in recent years have indicated that interactions between cancer cells and their microenvironment play a significant role at each stage of tumor progression [1]
We showed that calcitriol and its analogs stimulated the metastasis of 4T1 cells in young mice [9]
We showed that calcitriol and its analogs affect cancer progression in a different manner, depending on the age of the organism being studied
Summary
Numerous studies conducted in recent years have indicated that interactions between cancer cells and their microenvironment play a significant role at each stage of tumor progression [1]. Animal studies have shown that vitamin D supplementation in mouse feed or calcitriol administration inhibited tumor growth or metastasis in mice with human breast cancer xenograft [11,12], in allogenic transplant models [13,14], as well as in the MMTV-PyMT spontaneous mouse mammary gland cancer [15]. Our research group recently published a study in which we showed stimulation of metastasis after administration of calcitriol and its analogs in the 4T1 mouse model of breast cancer [9], while Cao et al reported a significant increase in tumor volume after vitamin D treatment [18]. It is postulated that vitamin D deficiency may promote the development of breast cancer and is usually associated with a poor prognosis [21,22]
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