INSERM-U981 Institut Gustave Roussy, Villejuif.
"Collective epithelial-based metastases in colorectal carcinoma patients"
As a critical step in cancer progression and a challenge to patient treatment, tumour cell dissemination has been the subject of intense investigation across a range of model systems, in vitro and in animals. These studies have led to the assumption that the fatal progression of carcinoma is associated with a loss of epithelial architecture and polarity1-3 as single tumour cells escape from the primary tumour to reach secondary sites4,5. However, these studies have been performed using experimental model systems and the mechanisms driving metastatic spread in cancer patients remain under-investigated. Here, we collected and monitored over 50 patient specimens ex vivo to investigate the cell biology of colorectal cancer (CRC) metastasis as it spreads to the peritoneum. This reveals a new mode of cancer dissemination. Large clusters of cancer epithelial cells displaying an inverted apico-basolateral polarity, which we term Tumour Spheres with Inverted Polarity (TSIPs), were observed throughout the process of tumour dissemination. We show that TSIPs form and propagate through the collective apical budding of hyper-methylated neoplastic tissues. Despite their inverted topology, TSIPs collectively invade extracellular matrices, paired patients¹ peritoneum explants and initiate metastases in mice xenograft models. Further, the presence of TSIPs in peritoneal effusions correlates with metastases burden and adverse patient prognosis. Thus, despite their having a robust epithelial architecture, TSIPs appear to drive the peritoneal dissemination of CRC, as well as other primary cancers, such as breast carcinoma. By applying cell biological methods to live primary cancer specimens, we provide an alternative conception of cancer dissemination that goes against the prevailing consensus and could not be anticipated from experimental model systems.
Department of Molecular and Translational Medicine, University of Brescia
"Stromal delivery of long Pentraxin-3 impairs FGF/FGFR-dependent tumor growth and metastasis"
The fibroblast growth factor (FGF)/FGF receptor (FGFR) system plays a crucial role in cancer by affecting tumor growth, angiogenesis, drug resistance and escape from anti-angiogenic anti-vascular endothelial growth factor therapy. The soluble pattern recognition receptor long-pentraxin 3 (PTX3) acts as a multi-FGF antagonist. In a recent study we demonstrated that local and systemic delivery of human PTX3 in transgenic mice driven by the endothelial specific Tie2 promoter inhibits tumor growth, angiogenesis and metastasis in heterotopic, orthotopic and autochthonous FGF-dependent tumor models. Moreover, NMR data and pharmacophore modeling of the interaction of a minimal PTX3-derived FGF-binding pentapeptide with FGF2 were used for the identification of the first small molecule chemical (NSC12) which acts as an orally active extracellular FGF trap with significant implications in cancer therapy. We are currently characterizing the role of PTX3 expression in different types of solid and hematological tumors.
Head of Artificial Intelligence and Gene Regulation, IGH, Montpellier
“Artificial Intelligence empowers transcriptomics but will ultimately cause its demise"
The seminar in short:
In my talk, I will show how simple information theory concepts such as entropy and information content allow scientists to better understand gene regulation in numerous types of disease. I will then demonstrate that recent advances in artificial intelligence approaches such as genetic programming and neural nets may be so powerful that they abrogate our need to understand these functions at all. Recent research in my team will show how AI allows us to explore sequencing data from cancer samples with no a priori and is more powerful than current approaches for classifying and predicting outcomes.
"Single cell transcriptomics and proteomics"
Résumé de la présentation : High-throughput, single-cell expression measurements enable discovery of gene expression dynamics for profiling individual cell types. The Chromium Single Cell Controller which is a dedicated instrument for single cell applications and features a simple and comprehensive workflow, enabling users to quickly and easily prepare single cell sequencing libraries in less than one workday.
With the unique ability to interrogate hundreds to millions of cells, the Single Cell Chromium Controller supports a variety of applications, including the existing Chromium™ Single Cell 3’ Solution, as well as a future product featuring to perform full-length sequencing of V(D)J segments from single B or T cells. The system is accompanied by Chromium Single Cell 3’ Reagent Kits with advanced chemistry and microfluidics consumables based on GemCode™ Technology and features full compatibility with the Illumina® HiSeq® 4000 and other HiSeq®, NovaSeq®, NextSeq® and MiSeq® sequencers.
Département d’Oncologie Moléculaire Institut Paoli Calmettes, Marseille
“Profilage oncogénomique des cancers avancés dans les essais PANDORA et PERMED à l’IPC"