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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma

Authors: Marieke L Kuijjer, Elisabeth FP Peterse, Brendy EWM van den Akker, Inge H Briaire-de Bruijn, Massimo Serra, Leonardo A Meza-Zepeda, Ola Myklebost, A Bassim Hassan, Pancras CW Hogendoorn, Anne-Marie Cleton-Jansen

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

High-grade osteosarcoma is an aggressive tumor most often developing in the long bones of adolescents, with a second peak in the 5th decade of life. Better knowledge on cellular signaling in this tumor may identify new possibilities for targeted treatment.

Methods

We performed gene set analysis on previously published genome-wide gene expression data of osteosarcoma cell lines (n=19) and pretreatment biopsies (n=84). We characterized overexpression of the insulin-like growth factor receptor (IGF1R) signaling pathways in human osteosarcoma as compared with osteoblasts and with the hypothesized progenitor cells of osteosarcoma – mesenchymal stem cells. This pathway plays a key role in the growth and development of bone. Since most profound differences in mRNA expression were found at and upstream of the receptor of this pathway, we set out to inhibit IR/IGF1R using OSI-906, a dual inhibitor for IR/IGF1R, on four osteosarcoma cell lines. Inhibitory effects of this drug were measured by Western blotting and cell proliferation assays.

Results

OSI-906 had a strong inhibitory effect on proliferation of 3 of 4 osteosarcoma cell lines, with IC50s below 100 nM at 72 hrs of treatment. Phosphorylation of IRS-1, a direct downstream target of IGF1R signaling, was inhibited in the responsive osteosarcoma cell lines.

Conclusions

This study provides an in vitro rationale for using IR/IGF1R inhibitors in preclinical studies of osteosarcoma.
Appendix
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Metadata
Title
IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma
Authors
Marieke L Kuijjer
Elisabeth FP Peterse
Brendy EWM van den Akker
Inge H Briaire-de Bruijn
Massimo Serra
Leonardo A Meza-Zepeda
Ola Myklebost
A Bassim Hassan
Pancras CW Hogendoorn
Anne-Marie Cleton-Jansen
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-245

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