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 cells and stromal cells was investigated by using a human myeloma cell line (OPM-2) and human umbilical vein endothelial cells (HUVECs). Adhesion of OPM-2 cells to HUVECs was found to be significantly augmented with treatment of OPM-2 cells with an alpha-glycosidase inhibitor, castanospermine (CSP). The treatment of OPM-2 cells with CSP resulted in alteration of oligosaccharide structures of cell surface glycoproteins particularly at molecular weight of 220 kD (GP220). To determine if GP220 was involved in the adhesion of OPM-2 cells to HUVECs, cell surface glycoproteins of HUVECs were labeled by biotin and were incubated with the PVDF membrane to which cell surface glycoproteins of OPM-2 cells were blotted. The biotinylated glycoproteins at the plasma membrane of HUVECs specifically bound to GP220 of OPM-2 cells. Purification and partial amino acid sequencing of GP220 revealed that GP220 had a structure homologous to cation-independent mannose 6-phosphate/insulin-like growth factor-II (CIM6P/IGF-II) receptor. Furthermore, an antibody against CIM6P/IGF-II receptor was reactive with GP220, indicating that GP220 was a CIM6P/IGF-II receptor. The adhesion of OPM-2 cells to HUVECs was inhibited by mannose 6-phosphate. Moreover, M6P was found to suppress 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 in response to IGF-II. These results suggest that CIM6P/IGF-II receptor may be functional in terms of supporting cell adhesion and proliferation of myeloma cells.
Second Department of Internal Medicine, Osaka University Medical School, Japan.
T
T
Nishiura
T
T
Karasuno
H
H
Yoshida
H
H
Nakao
M
M
Ogawa
Y
Y
Horikawa
M
M
Yoshimura
Y
Y
Okajima
Y
Y
Kanakura
Y
Y
Kanayama
Y
Y
Matsuzawa
D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008360:Mannosephosphates / Q000494:pharmacology; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate; D007335:Insulin-Like Growth Factor II