Figure 7.

The effect of calcitriol or its analogs on Th17 cells in young and aged mammary gland tumor-bearing mice. Young (~8 weeks old) or aged ovariectomized (~50 weeks old) BALB/c mice were transplanted orthotopically (ort.) with 4T1 mouse mammary gland cancer cells, and then injected s.c. with calcitriol or tacalcitol. Increased metastatic potential was observed in young mice treated with calcitriol or tacalcitol, whereas in aged mice decreased metastasis count was noticed. In young mice, lung tissue showed increased osteopontin gene (Spp1) expression with increased osteopontin (OPN) protein level and plasma level of 17β-estradiol and TGF-β, which may contribute to increased Th17 cell differentiation and increased metastatic spread of 4T1 tumors. In aged mice, OPN level in tumor tissue, as well as plasma level of OPN and 17β-estradiol, was decreased with lower IL-17A production by induced Th17 cells (iTh17), leading to decreased metastatic potential of 4T1 cells.