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

Endocrinology. 2002 Nov;143(11):4287-94. doi: 10.1210/en.2002-220548.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Division*
  • Choriocarcinoma / pathology*
  • DNA, Complementary / genetics
  • Gene Expression*
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / analysis
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • RNA, Messenger / analysis
  • Receptor, IGF Type 2 / blood
  • Receptor, IGF Type 2 / genetics*
  • Receptor, IGF Type 2 / physiology*
  • Transfection
  • Tumor Cells, Cultured


  • DNA, Complementary
  • Insulin-Like Growth Factor Binding Proteins
  • RNA, Messenger
  • Receptor, IGF Type 2