Cellular growth inhibition by IGFBP-3 and TGF-β1 requires LRP-1

Shuan Shian Huang, Thai Yen Ling, Wen Fang Tseng, Yen Hwa Huang, Fen Mei Tang, Sandra M. Leal, Jung San Huang

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

The type V TGF-β receptor (TβR-V)/ IGFBP-3 receptor mediates the IGF-independent growth inhibition induced by IGFBP-3. It also mediates the growth inhibitory response to TGF-β1 in concert with other TGF-β receptor types, and its loss may contribute to the malignant phenotype of human carcinoma cells. Here we demonstrate that TβR-V is identical to LRP-1/α2M receptor as shown by MALDI-TOF analysis of tryptic peptides of TβR-V purified from bovine liver. In addition, 125I-IGFBP-3 affinity-labeled TβR-V in Mv1Lu cells is immunoprecipitated by antibodies to LRP-1 and TβR-V. RAP, an LRP-1 antagonist, inhibits binding of 125I-TGF-β1 and 125I-IGFBP-3 to TβR-V and diminishes IGFBP-3-induced growth inhibition in Mv1Lu cells. Absent or low levels of LRP-1, as with TβR-V, have been linked to the malignant phenotype of carcinoma cells. Mutagenized Mv1Lu cells selected for reduced expression of LRP-1 have an attenuated growth inhibitory response to TGF-β1 and IGFBP-3. LRP-1-deficient mouse embryonic fibroblasts lack a growth inhibitory response to TGF-β 1 and IGFBP-3. On the other hand, stable transfection of H1299 human lung carcinoma cells with LRP-1 cDNA restores the growth inhibitory response. These results suggest that the LRP-1/TβR-V/IGFBP-3 receptor is required for the growth inhibitory response to IGFBP-3 and TGF-β1.

Original languageEnglish
Pages (from-to)2068-2081
Number of pages14
JournalFASEB Journal
Volume17
Issue number14
DOIs
Publication statusPublished - Nov 2003

Keywords

  • Carcinogenesis
  • Epithelial cells
  • Growth inhibition
  • IGFBP-3 receptor
  • Type V TGF-β receptor

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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  • Cite this

    Huang, S. S., Ling, T. Y., Tseng, W. F., Huang, Y. H., Tang, F. M., Leal, S. M., & Huang, J. S. (2003). Cellular growth inhibition by IGFBP-3 and TGF-β1 requires LRP-1. FASEB Journal, 17(14), 2068-2081. https://doi.org/10.1096/fj.03-0256com