Biology subjects

Gigoux, V.

Publications and source records attributed to Gigoux, V..

3 recordsLinked to original sources

bioRxiv2026

Origin of Fe ions in ROS production induced in magnetic hyperthermia anti-cancer nanotherapy: release from iron oxide nanoparticles or not?

The first and critical reaction in magnetic hyperthermia to induce the death of cancer cells is the production of ROS (reactive oxygen species). We previously showed that it is possible to specifically deliver iron oxide magnetic nanoparticles (IONPs) in the lysosomes of cancer cells and eradicate them by targeted magnetic intra-lysosomal hyperthermia (MILH) via the application of a high frequency alternating magnetic field (AMF) without macroscopic temperature elevation. The mechanism involves a local temperature elevation at the IONPs surface which enhances the ROS production through the Fenton reaction; ROS then peroxide the proteins and lipids of the lysosomal membrane, inducing its permeabilization and leading to lysosomal enzymes release and cell death. Fe ions, critical to produce ROS in MILH, were assumed to be released by IONPs. We thus developed PEGylated multi-cores IONPs called NanoFlowers (NF@PEG) presenting or not a SiO2 shell (NF@SiO2 @PEG), the later preventing the Fe3+ release from IONPs. NF@PEG released Fe ions and produced ROS production in vitro, in acidic medium mimicking lysosome upon AMF exposure, whereas NF@SiO2@PEG did not. Surprisingly, both nanoparticles increased the ROS production in cells, induced lysosome permeabilization and cell death, and slowed down the proliferation of cancer cells with the same efficacy, upon AMF application, indicating that MILH was efficient in absence of Fe3+ release from IONPs. In contrast, Ferristatin-II, an iron uptake inhibitor, prevented the ROS production and cell death in MILH induced by both IONPs, elucidating the role of endogenous iron cations responsible for the ROS production ROS in MILH to kill cancer cells.

cancer biology↗

bioRxiv2025

Targeting human M2 macrophages with antibodies in optimized 3D tumor spheroids

Tumor microenvironment (TME) constituents, including tumor-associated macrophages (TAMs), are now well known to have a significant impact on tumor development. TAMs can be predominant cells in the TME, able to promote cancer cell proliferation, resistance to treatments and immunosuppression. Inactivating these TAMs in tumors by their depletion or their repolarization into a specific anti-tumor, inflammatory phenotype constitutes a significant challenge in immuno-oncology. Several tools and methods to target TAMs have been proposed but they often show low specificity for pro-tumoral macrophages and target myeloid cells too broadly. This research area is therefore in full expansion and warrants the development of appropriate study models. Given the current global effort to reduce the use of in vivo approaches, developing in vitro models that mimic the behavior of TAMs in the TME has become a priority. In this study, we focused on targeting pro-tumoral TAMs in a simple in vitro model recapitulating cancer cell proliferation and TAMs specific phenotype. We developed a 3D model consisting of cancer cells and pro-tumoral macrophages, in which these macrophages promote tumor cell proliferation, maintaining an immunosuppressive phenotype. We showed that, in this model, macrophages can be easily targeted and killed with specific antibodies even in the central regions of the spheroid. This model could be a first in vitro approach to screen new TAM depletion or depolarization tools before application in in vivo models.

cancer biology↗

bioRxiv2023

The Loss of the E3 ubiquitin ligase TRIP12 inhibits Pancreatic Acinar Cell Plasticity and Tumor Cell Metastatic Capacity

Background & AimsAlthough specialized and dedicated to the production of digestive enzymes, pancreatic acinar cells harbor a high plasticity and are able to modify their identity. They undergo reversible acinar-to-ductal cell metaplasia (ADM) through epigenetic silencing of the acinar lineage gene program mainly controlled by PTF1a (Pancreas Transcription Factor 1a). ADM becomes irreversible in the presence of oncogenic Kras mutations and leads to the formation of preneoplastic lesions. We investigated the role of the E3 ubiquitin ligase Thyroid hormone Receptor Interacting Protein 12 (TRIP12), involved in PTF1a degradation, in pancreatic carcinogenesis. MethodsWe used genetically engineered mouse models of pancreas-selective Trip12 deletion, mutant Kras (G12D) and mutant Trp53 (R172H). We performed RNA sequencing analysis from acinar cells and cell lines derived from mice models tumors. We investigated the impact of TRIP12 deficiency on acute pancreatitis, tumor formation and metastasis development. ResultsTRIP12 is overexpressed in human pancreatic preneoplastic lesions and tumors. We show that a conditional deletion of TRIP12 in the pancreas during murine embryogenesis alters pancreas homeostasis and acinar cell genes expression patterns in adults. EGF induced-ADM is suppressed in TRIP12-depleted pancreatic acini. In vivo, a loss of TRIP12 prevents acini to develop ADM in response to pancreatic injury, the formation of Kras-induced pancreatic preneoplastic lesions, and impairs tumors and metastasis formation in the presence of mutated Trp53. TRIP12 is required for Claudin18.2 isoform expression in pancreatic tumors cells. ConclusionsOur study identifies TRIP12 as a novel regulator of acinar fate in the adult pancreas with an important dual role in pancreatic carcinogenesis, in initiation steps and in metastatic behavior of tumor cells. SynopsisThis study shows that Thyroid hormone Receptor Interacting Protein 12 plays an important dual role in the initiation steps and invasion of pancreatic carcinogenesis. Moreover, expression of TRIP12 switches on the expression of Claudin-18, a targetable biomarker of pancreatic tumors.

cancer biology↗