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/
T. Nishiura et al., 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/, Blood, 88(9), 1996, pp. 3546-3554
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.