Biology subjects

Lalloue, F.

Publications and source records attributed to Lalloue, F..

5 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2024

Predicting Tumor Mutational Burden from UHF-Dielectrophoresis Crossover Frequency

Tumor Mutational Burden (TMB) has emerged as a crucial biomarker to guide patient eligibility for immunotherapy. However, whole exome sequencing, the gold-standard method for TMB measurement, remains limited in accessibility due to its high costs, operational complexity, and lengthy processing times. To address these limitations, we investigated whether Ultra-High-Frequency (UHF) technology could serve as a novel approach to assess TMB by analyzing the crossover frequencies or electromagnetic signature (EMS) of cancer cells on a lab-on-a-chip biosensor, integrating microfluidics and dielectrophoresis. In a panel of 12 cancer cell lines with varying TMB levels, we observed that EMS showed an upward shift correlating with higher TMB, particularly in solid tumor cell lines. This finding suggests a potential relationship between TMB and EMS. To further explore this hypothesis, we artificially increased mutation levels by treating cells with the highly mutagenic compound N-ethyl-N-nitrosourea (ENU). Results showed that EMS captured significant TMB variations in ENU-treated cells with enhanced proliferative capacity compared to their parental counterparts. These results underscore the importance of matched control samples for reliable EMS measurements. Altogether, our findings highlight the potential of EMS to detect TMB variations associated with proliferative activity, a key hallmark of cancer cells, thereby enabling a more precise stratification of cancer cells. HighlightsO_LIWe propose a new biosensor to improve patient stratification for ICI eligibility C_LIO_LIHigh frequency fields and dielectric spectroscopy can estimate TMB in cancer cells C_LIO_LISignificant changes in UHF-DEP signatures correlate with varying TMB levels C_LIO_LIUHF-DEP provides a cheap, rapid and label-free method to predict ICI response C_LIO_LIOffers an innovative and complementary marker to conventional diagnostic approaches C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/622085v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@703983org.highwire.dtl.DTLVardef@1cfdf46org.highwire.dtl.DTLVardef@4b9285org.highwire.dtl.DTLVardef@1809255_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

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↗

bioRxiv2021

Radiotherapy induces specific miRNA expression profiles in glioblastoma exosomes

BackgroundGlioblastoma (GBM) is the most aggressive and frequent primary brain tumor during adulthood. One of the major treatments is the association of surgery and a combination of chemo and radiotherapies. Despite its immediate efficiency, it fails to prevent the cancer recurrence in the irradiated area due to radioresistance mechanisms. MicroRNAs (miRNAs or miR) are small non-coding, single strand RNA molecules encoding to various specific genes and able to regulate their expression and induce the tumor cell survival leading to radioresistance. Small extracellular vesicles (EVs), or exosomes released by tumor cells in tumor microenvironment and blood circulation are able to transport and diffuse miRNAs and affect the microenvironment by spreading the miRNAs, which drive radioresistance. AimsO_LITo identify the variations of miRNAs expression induced by irradiation in human glioblastoma U87-MG cells and their secreted exosomes collected in supernatants. C_LIO_LITo analyze the miRNAs variations in EVs-derived from the plasma of patients during radiotherapy, in order to identify a miRNA signature induced by radiotherapy in a liquid biopsy. C_LI Materiel and methodsU87-MG cells were cultured on plates and exposed to irradiation. miRNAs analyzes were performed in cells and in EVs isolated from cell supernatants to determine miRNAs expressions both in cells and in secreted exosomes before and after irradiation. Plasma-derived EVs were collected from 4 glioblastoma patients before and after surgery and radiotherapy treatments. ConclusionThe analysis of miRNAs expression profiles in both GBM cells and their derived EVs revealed that miR profile changes after irradiation. However, the number of similar miR between cells or EVs, following cell irradiation, was restricted to 3 miRs alone suggesting that the irradiation-induced changes in the miR profile in the cells and their EVs are not closely linked. In this context, the miR profile in EVs from patients plasma was investigated to establish a potential link with the miRNAs profile observed in EVs from irradiated cells and to assess its relationship with the response to radiotherapy. Three miRs (different from those identified in cells) were common between EVs derived from cells and patients derived-exosomes. These miRs detected in circulating EVs could provide a specific and reliable signature in response to ionizing radiation, which could be useful for monitoring the effectiveness of radiotherapy. Further experiments on a larger patients population with clinical data could also help to define whether this signature might have a prognostic value on the response to radiotherapy.

cancer biology↗

bioRxiv2021

Sortilin exhibits tumor suppressor-like activity by limiting EGFR transducing function

Lung cancer is the leading cause of cancer deaths worldwide and remains one of the most incurable. Tyrosine kinase receptors, such as the epidermal growth factor receptor (EGFR), are often aberrantly activated and drive tumor growth. Monotherapy with tyrosine kinase inhibitors to deactivate EGFR has shown initial efficacy, but their benefits tend to decline over time. EGFR acts as a transcriptional factor promoting the expression of co-oncogenic drivers, which, in turn, interact with canonical EGFR mutations to induce therapeutic relapse. This study reports that sortilin, a crucial regulator of cytoplasmic EGFR, attenuates its transducing function. Genome-wide chromatin binding revealed that sortilin interacts with gene regulatory elements occupied by EGFR. These results suggest a model, in which sortilin exhibits potential tumor suppressor-like activity by concurrently binding to regulatory elements of cMYC. Sortilin expression in lung adenocarcinoma may be predictive of the efficacy of anti-EGFR strategies.

cancer biology↗