Regulation of Tumor Cell Growth by the Mesenchymal Environment of the Bone Marrow is Enhanced by a High-Fat Diet

摘要

Obesity enhances prostate cancer (PC) metastasis to bone. Factors secreted from adipocytes enhance PC growth. We hypothesized that feeding a high fat diet to C57BL/6 mice would enhance bone marrow (BM) fibroblastic progenitor differentiation to adipocytes. Mice were fed isocaloric low (LFD) and high (HFD) fat diets for up to 11 weeks postweaning. BM cells were isolated and cultured in serum-free RPMI 1640 media (PC media), generating BM conditioned media (BM-CM). The HFD increased the adipocyte population. BM-CM-LFD inhibited LNCaP cell growth. The HFD partially reversed this suppression. Cytochrome P4501B1 (CYP1B1), which is expressed in BM and in prostate tumor stroma and epithelia, is suspected to influence PC. CYP1B1-/- BM-CM increased the proportion of DU145 cells in S-phase relative to C57BL/6 media. We conclude that BM cells secrete PC inhibitory paracrine factors, but also generate a stimulatory component in response to the HFD. CYP1B1 metabolism positively affects PC growth by metabolizing growth inhibitory factors.