In vivo induction of insulin-like growth factor-I receptor and CD44v6 confers homing and adhesion to murine multiple myeloma cells

One of the main characteristics of multiple myeloma (MM) cells is their spe cific homing and growth in the bone marrow (BM). Differences between stroma -dependent and -independent MM cell lines may reveal key molecules that pla y important roles in their homing to the BM. We addressed this topic with a murine MM model, including the in vivo 5T33MM (5T33MMvv) stroma-dependent cell line and its in vitro stroma-independent variant (5T33MMvt). Fluoresce nce-activated cell-sorting analysis showed expression of insulin-like growt h factor (IGF)-I receptor and CD44v6 on all 5T33MMvv cells but not on 5T33M Mvt cells. Checkerboard analysis and adhesion assays revealed IGF-I-depende nt chemotaxis toward BM-conditioned medium and involvement of CD44v6 in the adhesion to BM stroma of only 5T33MMvv cells. However, when 5T33MMvt cells were injected in vivo (5T33MMvt-vv), after 18 h the MM cells harvested fro m BM were IGP-I receptor and CD44v6 positive. This up-regulation was confir med in 5T33MMvt-vv cells isolated from terminally diseased animals. These 5 T33MMvt-vv cells exhibited IGF-I-dependent chemotaxis and CD44v6-dependent adhesion to BM stroma. In vitro culture of the 5T33MMvt-vv cells could comp letely down-regulate IGF-I receptor and CD44v6. In fact, we could show that direct contact of 5T33MMvt cells with BM endothelial cells is a prerequisi te for IGF-I receptor and CD44v6 up-regulation. These data indicate that th e BM microenvironment is capable of up-regulating molecules such as IGF-I r eceptor and CD44v6, which facilitate homing of MM cells to the BM and suppo rt their adhesion to BM stroma.