Insulin-like growth factor-binding protein-5 inhibits growth and induces differentiation of mouse osteosarcoma cells

Biochem Biophys Res Commun. 2001 Oct 26;288(2):435-42. doi: 10.1006/bbrc.2001.5785.


The precise role of insulin-like growth factor-binding protein-5 (IGFBP-5) in regulating the growth of tumor cells, especially of bone-derived malignant cells, is not well understood. We have investigated the biological activity of IGFBP-5 by transfecting OS/50-K8 mouse osteosarcoma cells with an expression vector containing the osteocalcin promoter and the complete mouse IGFBP-5 cDNA (OC-IGFBP-5). Overexpression of IGFBP-5 mRNA and secretion of increased amounts of bioactive protein in conditioned media were demonstrated in different clones. For the analysis of cell proliferation, three clones exhibiting high levels of IGFBP-5 expression were selected and compared to a mock clone and to nontransfected parental cells. IGFBP-5-secreting clones displayed reduced proliferation under both anchorage-dependent and -independent conditions (P < 0.05). The increase in proliferation observed in IGFBP-5-secreting clones after addition of exogenous IGF was significantly lower than that observed in mock-transfected or parental cells. A similar result was obtained with long[R3]IGF-I which has a low affinity for all IGFBPs, suggesting that the inhibitory effect of IGFBP-5 is only partially IGF-dependent. OC-IGFBP-5-transfected clones expressed significantly higher amounts of osteocalcin mRNA (P < 0.05) and secreted more osteocalcin protein than a mock clone or parental OS-50/K8 cells. Thus, part of the growth-inhibiting effect of IGFBP-5 may be due to an induction of differentiation in these cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Division / drug effects
  • Insulin-Like Growth Factor Binding Protein 5 / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Osteocalcin / metabolism
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Transfection
  • Tumor Cells, Cultured


  • Insulin-Like Growth Factor Binding Protein 5
  • RNA, Messenger
  • Osteocalcin