IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer
Abstract Background The insulin growth factor (IGF) pathway has been proposed as a potential therapeutic target in bladder cancer. We characterized the expression of components of the IGF pathway — insulin growth factor receptors (INSR, IGF1R, IGF2R), ligands (INS, IGF1, IGF2), and binding proteins...
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| Format: | Article |
| Language: | English |
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BMC
2017-09-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-017-3618-5 |
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| author | Yann Neuzillet Elodie Chapeaublanc Clémentine Krucker Leanne De Koning Thierry Lebret François Radvanyi Isabelle Bernard-Pierrot |
| author_facet | Yann Neuzillet Elodie Chapeaublanc Clémentine Krucker Leanne De Koning Thierry Lebret François Radvanyi Isabelle Bernard-Pierrot |
| author_sort | Yann Neuzillet |
| collection | DOAJ |
| description | Abstract Background The insulin growth factor (IGF) pathway has been proposed as a potential therapeutic target in bladder cancer. We characterized the expression of components of the IGF pathway — insulin growth factor receptors (INSR, IGF1R, IGF2R), ligands (INS, IGF1, IGF2), and binding proteins (IGFBP1–7, IGF2BP1–3) — in bladder cancer and its correlation with IGF1R activation, and the anti-proliferative efficacy of an IGF1R kinase inhibitor in this setting. Methods We analyzed transcriptomic data from two independent bladder cancer datasets, corresponding to 200 tumoral and five normal urothelium samples. We evaluated the activation status of the IGF pathway in bladder tumors, by assessing IGF1R phosphorylation and evaluating its correlation with mRNA levels for IGF pathway components. We finally evaluated the correlation between inhibition of proliferation by a selective inhibitor of the IGF1R kinase (AEW541), reported in 13 bladder cancer derived cell lines by the Cancer Cell Line Encyclopedia Consortium and mRNA levels for IGF pathway components. Results IGF1R expression and activation were stronger in non-muscle-invasive than in muscle-invasive bladder tumors. There was a significant inverse correlation between IGF1R phosphorylation and IGFBP5 expression in tumors. Consistent with this finding, the inhibition of bladder cell line viability by IGF1R inhibitor was also inversely correlated with IGFBP5 expression. Conclusion The IGF pathway is activated and therefore a potential therapeutic target for non muscle-invasive bladder tumors and IGFBP5 could be used as a surrogate marker for predicting tumor sensitivity to anti-IGF therapy. |
| first_indexed | 2024-04-12T12:12:25Z |
| format | Article |
| id | doaj.art-6166f90451174a048a406c55c1d81e6c |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T12:12:25Z |
| publishDate | 2017-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-6166f90451174a048a406c55c1d81e6c2022-12-22T03:33:32ZengBMCBMC Cancer1471-24072017-09-0117111210.1186/s12885-017-3618-5IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancerYann Neuzillet0Elodie Chapeaublanc1Clémentine Krucker2Leanne De Koning3Thierry Lebret4François Radvanyi5Isabelle Bernard-Pierrot6Hôpital Foch, Département d’UrologieInstitut Curie, PSL Research University, CNRS, UMR144, Equipe Labellisée Ligue contre le CancerInstitut Curie, PSL Research University, CNRS, UMR144, Equipe Labellisée Ligue contre le CancerInstitut Curie, PSL Research University, CNRS, UMR144, Equipe Labellisée Ligue contre le CancerHôpital Foch, Département d’UrologieInstitut Curie, PSL Research University, CNRS, UMR144, Equipe Labellisée Ligue contre le CancerInstitut Curie, PSL Research University, CNRS, UMR144, Equipe Labellisée Ligue contre le CancerAbstract Background The insulin growth factor (IGF) pathway has been proposed as a potential therapeutic target in bladder cancer. We characterized the expression of components of the IGF pathway — insulin growth factor receptors (INSR, IGF1R, IGF2R), ligands (INS, IGF1, IGF2), and binding proteins (IGFBP1–7, IGF2BP1–3) — in bladder cancer and its correlation with IGF1R activation, and the anti-proliferative efficacy of an IGF1R kinase inhibitor in this setting. Methods We analyzed transcriptomic data from two independent bladder cancer datasets, corresponding to 200 tumoral and five normal urothelium samples. We evaluated the activation status of the IGF pathway in bladder tumors, by assessing IGF1R phosphorylation and evaluating its correlation with mRNA levels for IGF pathway components. We finally evaluated the correlation between inhibition of proliferation by a selective inhibitor of the IGF1R kinase (AEW541), reported in 13 bladder cancer derived cell lines by the Cancer Cell Line Encyclopedia Consortium and mRNA levels for IGF pathway components. Results IGF1R expression and activation were stronger in non-muscle-invasive than in muscle-invasive bladder tumors. There was a significant inverse correlation between IGF1R phosphorylation and IGFBP5 expression in tumors. Consistent with this finding, the inhibition of bladder cell line viability by IGF1R inhibitor was also inversely correlated with IGFBP5 expression. Conclusion The IGF pathway is activated and therefore a potential therapeutic target for non muscle-invasive bladder tumors and IGFBP5 could be used as a surrogate marker for predicting tumor sensitivity to anti-IGF therapy.http://link.springer.com/article/10.1186/s12885-017-3618-5Bladder cancerOncogenesisIGFIGFRIGFBPIGF1R inhibitor |
| spellingShingle | Yann Neuzillet Elodie Chapeaublanc Clémentine Krucker Leanne De Koning Thierry Lebret François Radvanyi Isabelle Bernard-Pierrot IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer BMC Cancer Bladder cancer Oncogenesis IGF IGFR IGFBP IGF1R inhibitor |
| title | IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer |
| title_full | IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer |
| title_fullStr | IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer |
| title_full_unstemmed | IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer |
| title_short | IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer |
| title_sort | igf1r activation and the in vitro antiproliferative efficacy of igf1r inhibitor are inversely correlated with igfbp5 expression in bladder cancer |
| topic | Bladder cancer Oncogenesis IGF IGFR IGFBP IGF1R inhibitor |
| url | http://link.springer.com/article/10.1186/s12885-017-3618-5 |
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