FUNCTIONAL-ROLE OF CATION-INDEPENDENT MANNOSE 6-PHOSPHATE INSULIN-LIKE GROWTH-FACTOR-II RECEPTOR IN CELL-ADHESION AND PROLIFERATION OF A HUMAN MYELOMA CELL-LINE OPM-2/

The molecular mechanism underlying the interaction between myeloma cel ls and stromal cells was investigated by using a human myeloma cell li ne (OPM-2) and human umbilical vein endothelial cells (HUVECs). Adhesi on of OPM-2 cells to HUVECs was found to be significantly augmented wi th treatment of OPM-2 cells with an alpha-glycosidase inhibitor, casta nospermine (CSP). The treatment of OPM-2 cells with CSP resulted in al teration of oligosaccharide structures of cell surface glycoproteins p articularly at molecular weight of 220 kD (GP220). To determine if GP2 20 was involved in the adhesion of OPM-2 cells to HUVECs, cell surface glycoproteins of HUVECs were labeled by biotin and were incubated wit h the PVDF membrane to which cell surface glycoproteins of OPM-2 cells were blotted. The biotinylated glycoproteins at the plasma membrane o f HUVECs specifically bound to GP220 of OPM-2 cells. purification and partial amino acid sequencing of GP220 revealed that GP220 had a struc ture homologous to cation-independent mannose 6-phosphate-insulin-like growth factor-II (CIM6P/IGF-II) receptor. Furthermore, an antibody ag ainst CIM6P/IGFII receptor was reactive with GP220, indicating that GP 220 was a CIM6P/IGFII receptor. The adhesion of OPM-2 cells to HUVECs was inhibited by mannose S-phosphate. Moreover, M6P was found to suppr ess the adhesion of human myeloma cell lines, OPM-2 and RPMI 8226, to bone marrow stromal cells that was established from the patients with multiple myeloma, In addition, proliferation of OPM-2 was stimulated i n response to IGF-H. These results suggest that CIM6P/IGF-II receptor may be functional in terms of supporting cell adhesion and proliferati on of myeloma cells. (C) 1995 by The American Society of Hematology.