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Bone is a site of metastasis from several tumor types including prostate cancer (PCa). Metastatic PCa is lethal, largely due to the complex nature of bone microenvironment, and the functional cross-talk between bone-resident cells and tumor cells that favors therapy evasion. We have shown previously that age- and obesity-induced changes in the bone microenvironment, specifically increased marrow adiposity, promote tumor adaptation in bone. Numerous studies have also linked the disruption in bone homeostasis with aggressive tumor phenotype. Whether environmental toxicants with propensity to accumulate in bone can modulate bone microenvironment to support tumor growth and progression is, however, not known. Per- and polyfluoroalkyl substances (PFAS) are “forever” chemicals with very long half-lives and ability to accumulate in bone. Limited reports have linked PFAS exposure with adipocyte …