Interestingly, stromal signaling that drives differentiation of peripheral MDSCs may be bone marrow-derived: In transplantable models of lung carcinoma and melanoma (Lewis lung carcinoma and B16 melanoma cell lines), tumor-bearing mice had elevated systemic levels of Dickkopf-related protein 1 (Dkk1), which were found to originate in the bone stromal compartment (osteoblasts and osteocytes) (71). Here, DKK1 is linked to melanoma.