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Endocrinology. 2002 Nov;143(11):4287-94.

Insulin-like growth factor-II/mannose 6-phosphate receptor overexpression reduces growth of choriocarcinoma cells in vitro and in vivo.

Author information

1
Kolling Institute of Medical Research, University of Sydney and Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia.

Abstract

The IGF-II/mannose-6 phosphate receptor (IGF-II/M6PR) interacts with multiple tumor growth factors, including IGF-II and latent TGFbeta1. The IGF-II/M6PR has been proposed to be a tumor growth suppressor, a hypothesis supported by our previous finding that decreased IGF-II/M6PR expression enhances tumor growth. In this study, we further demonstrate that IGF-II/M6PR overexpression, resulting from cDNA transfection of JEG-3 choriocarcinoma cells, leads to a decreased cellular growth rate in vitro and decreased tumor growth in nude mice. Examination of several IGF-II/M6PR ligands in receptor-overexpressing cells showed no change in endogenous IGF-II or secretion of procathepsins D and L but an increase in latent TGFbeta1 secretion and activation. Cells transfected with cDNA for a truncated, soluble form of the receptor, previously shown to inhibit IGF-II-stimulated DNA synthesis, displayed a very slow growth rate in vitro and in nude mice but showed no alteration in TGFbeta1 levels. This suggests that, in IGFII/M6PR-transfected cells, increased levels of soluble IGF-II/M6PR may play a role in growth inhibition. Overall, the findings in this study are consistent with the hypothesis that the IGF-II/M6PR suppresses tumor growth.

PMID:
12399424
DOI:
10.1210/en.2002-220548
[Indexed for MEDLINE]

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