Abstract
Abstract Introduction: Malignant pleural mesothelioma (MPM) is one of the fatal cancers associated with asbestos exposure.Pemetrexed (PEM) is currently recommended as one of the antitumor drugs consisted of standard therapies for MPM.However, the mechanism of the sensitivity of MPM to PEM remains unclear. Methods: We analyzed the antitumor effects of PEM in six MPM cell lines by MTS assay. To identify genes associated with drug sensitivity,we conducted gene expression profiling on the same set of cell lines using Affymetrix HG-U133A GeneChips. Pathway analysis was performed to provide a viewpoint of the biological function of the genes. Results: Three cell lines were sensitive to PEM. Eighteen transcripts and fourteen genes identified by Gene-chips were significantly correlated with sensitivity to PEM. Pathway analysis revealed that SPP1/OPN was an important target in PEM sensitivity. Overexpression of SPP1 was observed in the sensitive cells by Western blotting. Introduction of SPP1 by lentiviral vector significantly enhanced the invasion activities of MPM cells. Expression of SPP1/OPN and AKT phosphorylation were significantly decreased after PEM treatment of the PEM-sensitive cells. PEM treatment with SPP1/OPN knockdown inhibited the PEM-induced cell growth inhibitory effect in PEM-sensitive cells. Conclusions: Our results suggest that SPP1 may be used as a single predictive biomarker of the effectiveness of PEM treatment in MPM. Patient selection based on SPP1/OPN expression may be useful for future clinical development of PEM therapy for MPM. Citation Format: Masahiro Seike, Susumu Takeuchi, Chie Soeno, Rintaro Noro, Yuji Minegishi, Akihiko Gemma. Significance of osteopontin in the sensitivity of malignant pleural mesothelioma cells to pemetrexed. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3541. doi:10.1158/1538-7445.AM2013-3541
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