Insulin-like growth factor-binding protein-2 inhibits proliferation of human embryonic kidney fibroblasts and of IGF-responsive colon carcinoma cell lines

FEBS Lett. 1998 Sep 4;434(3):329-34. doi: 10.1016/s0014-5793(98)01011-4.

Abstract

So far, the physiological role of insulin-like growth factor binding protein-2 (IGFBP-2) has not been demonstrated directly. Therefore, we transfected 293 cells with an expression vector containing the CMV promoter and the complete cDNA of mouse IGFBP-2. Secretion of bioactive IGFBP-2 into conditioned medium was demonstrated by Western ligand and Western immunoblotting and quantified by specific RIA. For the analysis of cell proliferation three clones exhibiting either high or low/no IGFBP-2 expression were selected and compared to non-transfected parental 293 cells. IGFBP-2 secreting clones displayed reduced conversion of thiazolyl blue when compared to negative clones or non-transfected parental 293 cells (P < 0.01). The lower growth activity measured in the IGFBP-2 secreting clones was compensated in great part by the administration of exogenous IGF-I or -II. Conditioned media of IGFBP-2 secreting clones inhibited growth of IGF-responsive colon tumor cell lines (LS513, HT-29) while those of negative clones did not. In addition, conditioned medium from a clone expressing high levels of IGFBP-2 inhibited anchorage-independent growth of LS513 and HT-29 cells. In contrast, growth of an IGF-unresponsive tumor cell line (Co-115) was not affected by the conditioned media. We hypothesize that IGFBP-2 might sequester the IGFs and thus prevent them from transferring their mitogenic signals.

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Division / physiology
  • Cell Line
  • Clone Cells
  • Colonic Neoplasms / pathology*
  • Culture Media, Conditioned
  • Fibroblasts / cytology
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / genetics
  • Insulin-Like Growth Factor Binding Protein 2 / physiology*
  • Kidney / cytology*
  • Kidney / embryology
  • Mice
  • RNA, Messenger / genetics
  • Somatomedins / physiology*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Culture Media, Conditioned
  • Insulin-Like Growth Factor Binding Protein 2
  • RNA, Messenger
  • Somatomedins