Expression and Down‐Regulation by Retinoic Acid of IGF Binding Protein‐2 and ‐4 in Medium from Human Neuroblastoma Cells

Sergio Bernardini, Stefano Cianfarani, Anna Spagnoli, Margherita Annicchiarico‐Petruzzelli, Gerry Melino, Renato Massoud, Brunetto Boscherini, Alessandro Finazzi‐Agró, Ron G. Rosenfeld, Giorgio Federici

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Insulin‐like growth factors (IGFs) regulate the autocrine/paracrine growth of neuroblastomas. The IGFs bind to specific binding proteins (IGFBPs) which modulate their biological activity. We investigated, by Western ligand blotting (WLB), the presence of IGFBPs and their possible modulation by retinoic acid (RA), IGF‐I, IGF‐II and truncated Des(1‐3)IGF‐l in conditioned medium (CM) of the human neuroblastoma SK‐N‐BE(2) cell line. We demonstrated the presence of two IGFBPs, with MW 37 kDa and 25 kDa. Following immunoprecipitation, they turned out to be IGFBP‐2 and ‐4, respectively. The RA‐induced differentiation in SK‐N‐BE(2) cells was accompanied by a marked reduction of the intensity of both IGFBP bands after 48 h (32% and 24% of control, respectively) and 72 h (2% and 0% of control, respectively) incubation. The addition of exogenous IGFs, which did not induce cell differentiation, did not change the IGFBP pattern significantly, except for the truncated form of IGF‐I, which induced a marked decrease in both the 37 kDa and 25kDa bands after 72 h incubation (45% and 18% of control, respectively). These findings suggest that IGFBPs have a role in RA‐induced differentiation in human neuroblastoma cells.

Original languageEnglish (US)
Pages (from-to)409-413
Number of pages5
JournalJournal of Neuroendocrinology
Issue number4
StatePublished - Aug 1994
Externally publishedYes


  • insulin‐like growth factors
  • insulin‐like growth factor‐binding proteins
  • neuroblastoma
  • retinoic acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience


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