TY - JOUR AB - Low vitamin D status is considered as a risk factor for breast cancer and has prognostic significance. Furthermore, vitamin D deficiency increases after adjuvant cancer therapy, which alters bone metabolism increasing the risk of osteoporosis. It is now postulated that vitamin D supplementation in breast cancer treatment delays the recurrence of cancer thereby extending survival. We evaluated the impact of calcitriol and its low-calcemic analogs, PRI‑2191 and PRI‑2205, on the tumor growth, angiogenesis, and metastasis of 4T1 mouse mammary gland cancer. Gene expression analysis related to cancer invasion/metastasis, real‑time PCR, ELISA, western blotting, and histochemical studies were performed. In vitro studies were conducted to compare the effects of calcitriol and its analogs on 4T1 and 67NR cell proliferation and expression of selected proteins. Calcitriol and its analogs increased lung metastasis without influencing the growth of primary tumor. The levels of plasma 17β-estradiol and transforming growth factor β (TGFβ) were found to be elevated after treatment. Moreover, the results showed that tumor blood perfusion improved and osteopontin (OPN) levels increased, whereas vascular endothelial growth factor (VEGF) and TGFβ levels decreased in tumors from treated mice. All the studied treatments resulted in increased collagen content in the tumor tissue in the early step of tumor progression, and calcitriol caused an increase in collagen content in lung tissue. In addition, in vitro proliferation of 4T1 tumor cells was not found to be affected by calcitriol or its analogs in contrast to non-metastatic 67NR cells. Calcitriol and its analogs enhanced the metastatic potential of 4T1 mouse mammary gland cancer by inducing the secretion of OPN probably via host cells. In addition, OPN tumor overexpression prevailed over the decreasing tumor TGFβ level and blood vessel normalization via tumor VEGF deprivation induced by calcitriol and its analogs. Moreover, the increased plasma TGFβ and 17β-estradiol levels contributed to the facilitation of metastatic process. AD - Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53‑114 Wroclaw, Poland Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland Department of Pharmacology, Pharmaceutical Research Institute, 01-793 Warsaw, Poland Université Clermont Auvergne, INRA, UNH, F-63000 Clermont-Ferrand, France AU - Anisiewicz,Artur AU - Pawlik,Agata AU - Filip-Psurska,Beata AU - Turlej,Eliza AU - Dzimira,Stanisław AU - Milczarek,Magdalena AU - Gdesz,Katarzyna AU - Papiernik,Diana AU - Jarosz,Joanna AU - Kłopotowska,Dagmara AU - Kutner,Andrzej AU - Mazur,Andrzej AU - Wietrzyk,Joanna DA - 2018/01/01 DO - 10.3892/ijo.2017.4185 EP - 126 IS - 1 JO - Int J Oncol KW - metastasis calcitriol analog 4T1 mouse mammary gland cancer osteopontin TGFβ PY - 2018 SN - 1019-6439 1791-2423 SP - 103 ST - Unfavorable effect of calcitriol and its low-calcemic analogs on metastasis of 4T1 mouse mammary gland cancer T2 - International Journal of Oncology TI - Unfavorable effect of calcitriol and its low-calcemic analogs on metastasis of 4T1 mouse mammary gland cancer UR - https://doi.org/10.3892/ijo.2017.4185 VL - 52 ER -