title: In vivo induction of insulin-like growth factor-I receptor and CD44v6 confers homing and adhesion to murine multiple myeloma cells.
abstract: One of the main characteristics of multiple myeloma (MM) cells is their specific homing and growth in the bone marrow (BM). Differences between stroma-dependent and -independent MM cell lines may reveal key molecules that play 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). Fluorescence-activated cell-sorting analysis showed expression of insulin-like growth factor (IGF)-I receptor and CD44v6 on all 5T33MMvv cells but not on 5T33MMvt cells. Checkerboard analysis and adhesion assays revealed IGF-I-dependent 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 from BM were IGF-I receptor and CD44v6 positive. This up-regulation was confirmed in 5T33MMvt-vv cells isolated from terminally diseased animals. These ST33MMvt-vv cells exhibited IGF-I-dependent chemotaxis and CD44v6-dependent adhesion to BM stroma. In vitro culture of the 5T33MMvt-vv cells could completely down-regulate IGF-I receptor and CD44v6. In fact, we could show that direct contact of 5T33MMvt cells with BM endothelial cells is a prerequisite for IGF-I receptor and CD44v6 up-regulation. These data indicate that the BM microenvironment is capable of up-regulating molecules such as IGF-I receptor and CD44v6, which facilitate homing of MM cells to the BM and support their adhesion to BM stroma.
authors.affiliation: Department of Hematology and Immunology, Free University Brussels, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Asosingh
authors.forename: U
authors.initials: U
authors.lastname: Günthert
authors.forename: M H
authors.initials: MH
authors.lastname: Bakkus
authors.forename: H
authors.initials: H
authors.lastname: De Raeve
authors.forename: E
authors.initials: E
authors.lastname: Goes
authors.forename: I
authors.initials: I
authors.lastname: Van Riet
authors.forename: B
authors.initials: B
authors.lastname: Van Camp
authors.forename: K
authors.initials: K
authors.lastname: Vanderkerken
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D002633:Chemotaxis; D015536:Down-Regulation; D004727:Endothelium / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000378:metabolism*; D009368:Neoplasm Transplantation; D020033:Protein Isoforms; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D015854:Up-Regulation
chemical_list: C112697:CD44v6 antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D017526:Receptor, IGF Type 1