The insulin-like growth factor II (IGF-II)/mannose 6-phosphate receptor mediates IGF-II-induced motility in human rhabdomyosarcoma cells.
Insulin-like growth factor-II (IGF-II) is an autocrine growth and motility factor for human rhabdomyosarcoma. It interacts with three different receptors: the IGF-I, the IGF-II, and the insulin receptor. A specific function of the IGF-II receptor in mediating IGF-II responses has not been defined. In this report we investigate the mechanism of IGF-II-mediated motility in rhabdomyosarcoma cells. We demonstrate that IGF-II and [Leu27]IGF-II, an analog selective for the IGF-II receptor, stimulate motility at concentrations in which they interact only with their own receptor. An antibody that blocks the IGF-I receptor does not inhibit either peptide activity, while an antibody specific for the IGF-II receptor suppresses the IGF-II-induced motility. This antibody does not interfere with rhabdomyosarcoma cell proliferation. We conclude that in rhabdomyosarcoma cells IGF-II stimulates two different responses mediated by distinct receptors: 1) a mitogenic response through the type I receptor and 2) a motility response through the type II receptor.
Minniti
C P
CP
Molecular Genetics Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Kohn
E C
EC
Grubb
J H
JH
Sly
W S
WS
Oh
Y
Y
Müller
H L
HL
Rosenfeld
R G
RG
Helman
L J
LJ
D000345:Affinity Labels; D002465:Cell Movement; D003432:Cross-Linking Reagents; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000031:analogs & derivatives / Q000378:metabolism*; D008360:Mannosephosphates / Q000378:metabolism*; D011869:Radioligand Assay; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012208:Rhabdomyosarcoma; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000345:Affinity Labels; D003432:Cross-Linking Reagents; D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; C027693:mannose-6-phosphate; D007335:Insulin-Like Growth Factor II