Biology subjects

Cochet, C.

Publications and source records attributed to Cochet, C..

4 recordsLinked to original sources

bioRxiv2025

Using 3D Invasion properties of RCC Cell Lines In Vitro to predict their Metastatic Potential In Vivo

Renal cell carcinoma (RCC) exhibits significant heterogeneity, making it challenging to predict tumor aggressiveness and therapeutic response. To improve prognostic accuracy and develop tailored treatment strategies, it is crucial to mimic both cancer cells and their microenvironment in vitro. Using a combination of in vitro and in vivo models, we investigated the invasive properties of three RCC cell lines--RCC10, RCC7 and 786-O-- that displayed distinct signaling profiles, combining EMT characteristics and upregulation of key metastatic markers. Our findings revealed that RCC7 and 786-O exhibited greater metastatic potential than RCC10, as demonstrated by increased extravasation in zebrafish embryos and higher lung metastases in the chorioallantoic membrane (CAM) and mice models. Comparative pathway analysis indicated that RCC7 displays partial epithelial-mesenchymal transition (pEMT) characteristics and upregulates key metastatic markers. Furthermore, our 3D spheroid invasion model as well as our patient-derived RCC tumoroid system predicted accurately their metastatic behavior, closely mirroring their aggressiveness in vivo. Thus, these 3D models might be predictive of tumor outcome, underscoring their utility as reliable predictive tools for RCC progression and therapeutic response. Novelty and ImpactNon-uniform distribution of genetic and phenotypic subpopulations within RCC tumors causes many tumors of similar histological grade to have vastly different metastatic potential. We show that 3D spheroids and RCC patient-derived tumoroid models more accurately reflect in vivo invasive behavior than traditional 2D assays, providing powerful predictive tools for RCC aggressiveness and metastatic disease. These findings have significant implications for precision oncology, enabling better preclinical evaluation of the metastatic risk to the patient.

cell biology↗

bioRxiv2024

Improving the monitoring of the invasive Blue Crab (Callinectes sapidus): combining environmental DNA and citizen observations

O_LIEarly detection is a crucial tool for identifying the spread of invasive species. C_LIO_LIIn this study, we validated a probe-based quantitative polymerase chain reaction (qPCR) assay for the detection of the invasive Blue Crab, Callinectes sapidus, in the Mediterranean Sea, using 22 initial eDNA environmental samples (eDNA) collected from three coastal lagoons. C_LIO_LIA subsequent large-scale eDNA sampling campaign (61 samples in 31 sites), conducted in collaboration with local stakeholders, was carried out to map the distribution of Callinectes sapidus along the Occitanie coastline (Western Mediterranean, France). C_LIO_LIUsing eDNA probe-based qPCR, Callinectes sapidus was detected in 32 out the 61 samples (52%), confirming its presence in 24 out of 31 sites surveyed, including the 13 lagoons where its occurrence had already been reported, as well as two additional lagoons and at sea where no prior records existed. C_LIO_LIOur results demonstrate the utility of eDNA probe-based qPCR for effective monitoring the invasive Blue Crab. The integration of eDNA analysis with citizen science observations enhances the monitoring framework, facilitating early detection and contributing to improved management strategies at the very beginning of species colonization when practical actions could be implemented. C_LI

ecology↗

bioRxiv2023

COL7A1 expression improves prognosis prediction for patients with clear cell renal cell carcinoma atop of stage

Clear cell renal cell carcinoma (ccRCC) accounts for 75% of kidney cancers. Due to the high recurrence rate, and treatment options that come with high costs and potential side effects correct prognosis of patient survival is essential for the successful and effective treatment of patients. Novel biomarkers could play an important role in the assessment of the overall survival of patients. COL7A1 encodes for collagen type VII, a constituent of the basal membrane. COL7A1 is associated with survival in many cancers; however, the prognostic value of COL7A1 expression as a standalone biomarker in ccRCC has not been investigated. We used Kaplan-Meier curves and Cox proportional hazards model to investigate the prognostic value of COL7A1, as well as Gene Set Enrichment Analysis to investigate genes that are co-expressed with COL7A1. COL7A1 expression was used to stratify patients into four groups of expression, where the 5-year survival probability of each group was 72.4%, 59.1%, 34.15%, and 8.6% in order of increasing expression. Additionally, COL7A1 expression was successfully used to further divide patients of each stage and histological grade into groups of high and low risk. Similar results were obtained in independent cohorts. In-vitro knockdown of COL7A1 expression significantly impacted ccRCC cells ability to migrate and proliferate. To conclude, we identified COL7A1 as a new prognosis marker that can stratify ccRCC patients.

cancer biology↗

bioRxiv2022

AB668, a novel highly selective protein kinase CK2 inhibitor with a distinct anti-tumor mechanism as compared to CX-4945 and SGC-CK2-1

Although the involvement of protein kinase CK2 in cancer is well-documented, there is a need for selective CK2 inhibitors suitable for investigating CK2 specific roles in cancer-related biological pathways and further explore its therapeutic potential. Here we have discovered AB668, a new bivalent inhibitor that binds both at the ATP site and an allosteric D pocket unique to CK2. The molecule inhibits CK2 activity with an outstanding selectivity over other kinases. Using caspase activation assay, live-cell imaging and transcriptomic analysis, we have compared the effects of this bivalent inhibitor to the non-selective ATP-competitive inhibitor CX-4945 that reached clinic and to the selective ATP-competitive SGC-CK2-1 molecule. Our results show that in contrast to CX-4945 or SGC-CK2-1, AB668 has a distinct mechanism of action regarding its anti-cancer activity, inducing apoptotic cell death and stimulating distinct biological pathways in several cancer cell lines while sparing healthy cells. Our data suggest that targeting a cryptic CK2 D pocket validates an allosteric approach to targeting CK2 and provides a starting point for creating drug-like CK2 inhibitors for aggressive cancers.

biochemistry↗