Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression from H69M versus H69 SCLC cell lines

ABSTRACT: H69M cells derive from H69 small cell lung cancer cells subjected to prolonged treatment with HGF. Among the whole population of cells, a subset of more fibroblastic cells was isolated (H69M-mesenchymal). In this experiment we compared expression profiles of both cell lines Keywords: Expression Profiling by array We analyzed 3 arrays from each condition:H69 versus H69M SCLC cell lines

ORGANISM(S): Homo sapiens

SUBMITTER: EDURNE ARRIOLA

PROVIDER: E-GEOD-45120 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Targeting epithelial-to-mesenchymal transition with Met inhibitors reverts chemoresistance in small cell lung cancer.

Cañadas Israel I Rojo Federico F Taus Álvaro Á Arpí Oriol O Arumí-Uría Montserrat M Pijuan Lara L Menéndez Silvia S Zazo Sandra S Dómine Manuel M Salido Marta M Mojal Sergi S García de Herreros Antonio A Rovira Ana A Albanell Joan J Arriola Edurne E

Clinical cancer research : an official journal of the American Association for Cancer Research 20131127 4

<h4>Purpose</h4>Met receptor phosphorylation is associated with poor prognosis in human small cell lung cancer (SCLC). The aim of our work was to investigate the effects of hepatocyte growth factor (HGF)/Met-mediated epithelial-to-mesenchymal transition (EMT) in SCLC and to evaluate the role of Met inhibition in mesenchymal/chemorefractory SCLC models.<h4>Experimental design</h4>SCLC models of HGF-induced EMT were evaluated in vitro and in vivo (subcutaneous xenografts in BALB/c nude mice) for c ...[more]

PMID: 24284055

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Project description:Insulin-like growth factor receptor-1 (IGF-1R) inhibition could be a relevant therapeutic approach in small cell lung cancer (SCLC) given the importance of an IGF-1R autocrine loop and its role in DNA damage repair processes. We assessed IGF-1R and pAkt protein expression in 83 SCLC human specimens. The efficacy of R1507 (a monoclonal antibody directed against IGF-1R) alone or combined with cisplatin or ionizing radiation (IR) was evaluated in H69, H146 and H526 cells in vitro and in vivo. Innovative genomic and functional approaches were conducted to analyze the molecular behavior under the different treatment conditions. A total of 53% and 37% of human specimens expressed IGF-1R and pAkt, respectively. R1507 demonstrated single agent activity in H146 and H526 cells but not in H69 cells. R1507 exhibited synergistic effects with both Cisplatin and IR in vitro. The triple combination R1507-Cisplatin-IR led to a dramatic delay in tumor growth compared to Cisplatin-IR in H526 cells. Analyzing the apparent absence of antitumoral effect of R1507 alone in vivo, we observed a transient reduction of IGF-1R staining intensity in vivo, concomitant to the activation of multiple cell surface receptors and intracellular proteins involved in proliferation, angiogenesis and survival. Finally, we identified that the nucleotide excision repair pathway (NER) was mediated after exposure to R1507-CDDP and R1507-IR in vitro and in vivo. In conclusion, adding R1507 to the current standard Cisplatin-IR doublet reveals remarkable chemo- and radiosensitizing effects in selected SCLC models and warrants to be investigated in the clinical setting. We used microarrays to investigate the effect of IGF-1R targetting on the global gene expression. Gene expression data from H526 xenografts under various treatment and time conditions Total mRNA from 33 NCI-H526 SCLC (small-cell lung cancer) xenografts was hybridized to Affymetrix HGU133 Plus 2.0 expression arrays. Log2 gene expression values were calculated using RMA. (A) To identify the molecular mechanisms involved in the response to R1507 alone along the treatment time, we performed global gene expression profiling in H526 xenografts at the following time points: baseline (vehicle), R1507 day 1 and R1507 day 7. (B) To identify the molecular mechanisms involved in the response to CDDP- and IR-R1507 combinations, we performed global gene expression profiling on mice bearing H526 xenografts treated with the following treatment conditions: vehicle, R1507 CDDP, IR, CDDP-R1507 and IR-R1507.

Dataset Information

Gene expression from H69M versus H69 SCLC cell lines

Publications

Targeting epithelial-to-mesenchymal transition with Met inhibitors reverts chemoresistance in small cell lung cancer.

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