By using measurements of osteoblast and osteoclast differentiation and function in vitro and a mouse model of skeletal metastasis, it was demonstrated that both soluble Sema4D (semaphoring 4D)and protein, an immune semaphore expressed by T-lymphocytes and eosinophils and to a lesser extent by dendritic cells and B-lymphocytes, produced by the breast cancer cell line, inhibit the differentiation of osteoblast cells, while Sema4D-mediated induction of IL-8 and LIX/CXCL5 (C-X-C motif chemokine 5), the murine homologue of IL-8, increases osteoclast numbers and activity [37]. Here, SEMA4D is linked to breast cancer.