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Gateau, A.

Publications and source records attributed to Gateau, A..

2 recordsLinked to original sources

Effects of panitumumab on the proteome of treated EGFRvIII glioblastoma cells and on their extracellular vesicles

Glioblastoma (GB) is an aggressive brain tumor for which reliable biomarkers of therapeutic response are still needed. Extracellular vesicles (EVs) can carry molecular components derived from their parent cells, thereby providing information on changes associated with the tumor and treatments. Among potential biomarkers, epidermal growth factor receptor variant III (EGFRvIII), is found in more than 40% of GB patients and is associated with aggressive tumor behavior and therapeutic resistance. EGFRvIII has also been detected on the surface of EVs, suggesting its potential value for monitoring tumor-associated molecular changes. This study investigated the effects of panitumumab, an anti-EGFR monoclonal antibody, on the proteomic profiles of EVs derived from EGFRvIII cells. U87 and U87-EGFRvIII cells and their derived EVs were characterized before and after treatment. EGFRvIII expression in cells and EVs was assessed by Western blotting and flow cytometry. Proteomic analyses were performed on cell lysates and EVs before and after treatment. Our results demonstrate that panitumumab significantly reduced surface EGFRvIII on EVs derived from U87-EGFRvIII cells, whereas no significant decrease was observed in cell lysates. This suggests that treatment may affect EGFRvIII trafficking or its incorporation into EVs. The proteomic analysis highlighted much more changes in EVs than in their parental cells after treatment, particularly in proteins associated with extracellular matrix organization and collagen. Together, these results demonstrate that panitumumab treatment is associated with changes in protein profile from EVs derived from EGFRvIII cells suggesting that the panitumumab treatment might have an impact on cells that could be reflected on EVs released by glioblastoma cells. In conclusion, our results suggest that EVs derived from EGFRvIII cells could serve as a useful circulating biomarker for assessing treatment efficacy and for preventing treatment escape.

cancer biology↗

New proteomic signature in circulating extracellular vesicles from tumor-draining vein of lung adenocarcinomas patients

Identification of noninvasive prognostic biomarkers, allowing monitoring of frequently developed relapse in patients with locally advanced non-small cell lung cancer (NSCLC), still of primary importance. Tumor-draining vein (TDV) plasma samples, are known to be enriched in circulating cancer biomarkers compared to samples from peripheral vein (PV). Thus, we thought to investigate the proteomic profile of extracellular vesicles (EVs) from TDV compared to those from PV plasma samples of patients operated for NSCLC. Purified EVs from TDV and PV plasma samples were characterized for their size distribution and concentration using nanoparticles tracking analysis (NTA). Proteomic profiling of TDV-derived EVs and PV-derived EVs were further done using mass spectrometry (nanoLC-MS/MS) analysis. In parallel, proteomic profile of tumoral and non-tumoral adjacent counterpart tissues from patients with NSCLC were investigated. Twenty patients with NSCLC, treated by surgery with curative intent, were enrolled in this study. We showed that EVs from TDV plasma samples were significantly smaller than those from PV plasma samples. Interestingly, the concentration of TDV-derived EVs were significantly higher than PV-derived EVs. However, EVs concentration and size were not associated with tumor size or other clinical characteristics. Proteomic profiling showed that 9 of the 10 most overexpressed proteins in EVs from TDV samples compared to those from PV, were associated with lung cancer diagnosis and prognosis. Remarkably, 1 protein (SRPRB) was commonly upregulated in lung tumor tissues (as compared to non-tumoral counterparts) and in TDV-derived EVs (as compared to PV-derived EVs). In contrast, 12 proteins were found to be upregulated in TDV-derived EVs and downregulated in tumor tissues. In conclusion, all of these identified proteins, carried by EVs from TDV plasma samples, might represent promising novel biomarkers for NSCLC prognosis and predicting recurrences at early stages.

cancer biology↗