SPP1 and breast cancer: Interestingly, tacalcitol increased the percentage of CD3+CD4+IL-17+ cells in the lungs of young 4T1 tumor-bearing mice while decreasing their percentage in aged OVX mice, aligning with the observed lung Spp1 expression.22,35 IL-17, through NF-κB-mediated expression of MMP-2 and MMP-9, is a key driver of breast cancer invasiveness and metastasis.41,42 Furthermore, OPN is known to promote Th17 lymphocytes and inflammation.28,43