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Decreased insulin-like growth factor-II/mannose 6-phosphate receptor expression enhances tumorigenicity in JEG-3

D B O'Gorman1, M Costello, J Weiss

  • 1Kolling Institute of Medical Research, University of Sydney and Royal North Shore Hospital, St. Leonards, NSW, Australia.

Cancer Research
|December 3, 1999
PubMed

Insights

The insulin-like growth factor-II/mannose-6 phosphate receptor (IGF-II/M6PR) normally inhibits tumor growth. Reducing IGF-II/M6PR levels accelerates tumor cell proliferation and growth, supporting its role as a tumor suppressor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The insulin-like growth factor-II/mannose-6 phosphate receptor (IGF-II/M6PR) binds and degrades IGF-II, a mitogen implicated in tumor growth.
  • Loss or mutation of IGF-II/M6PR in various tumors suggests its function as a negative regulator of cell growth.

Purpose of the Study:

  • To investigate the role of IGF-II/M6PR in tumor growth regulation.
  • To determine the effect of decreased IGF-II/M6PR expression on cell and tumor growth.

Main Methods:

  • Down-regulation of IGF-II/M6PR using antisense IGF-II/M6PR cDNA transfection in JEG-3 choriocarcinoma cells.
  • Assessment of in vitro cell growth rate.
  • Evaluation of in vivo tumor growth rate.

Main Results:

  • Down-regulation of IGF-II/M6PR led to an increased growth rate of JEG-3 cells in vitro.
  • Reduced IGF-II/M6PR expression resulted in an increased tumor growth rate in vivo.
  • These results indicate that decreased IGF-II/M6PR expression confers a growth advantage.

Conclusions:

  • The findings support the hypothesis that IGF-II/M6PR acts as an inhibitor of tumor growth.
  • A decrease in IGF-II/M6PR expression promotes tumor progression.
  • IGF-II/M6PR is a potential therapeutic target for cancer treatment.

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