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Invasion Mechanisms in Angiogenesis and Cancer team (IMAC)

Published on 31 January 2019



Team leader

Isabelle Vilgrain
Phone: 04 38 78 92 72
Fax: 04 38 78 49 64


Address

Laboratoire Biologie du Cancer et de l'Infection
CEA-Grenoble
17 avenue des Martyrs
38 054 Grenoble cedex 9
France


Members of the team



Nadia Alfaidy, Inserm researcher
Laurence Bouillet, PU-PH Grenoble University Hospital
Sophie Brouillet, HU assistant-Grenoble University
Olivier Chabre, PU-PH Grenoble University
Nadia Cherradi, Inserm researcher
Claude Cochet, Inserm researcher
Josiane Denis, Research engineer
Odile Filhol-Cochet, Inserm researcher
Laurent Guyon, CEA researcher
Pascale Hoffmann, PU-PH Grenoble University
Rémy Jardiller, PhD student
Déborah Reynaud, PhD student
Aude Salomon, Inserm assistant engineer
Frédéric Sergent, Technicien CEA
Isabelle Vilgrain, CNRS researcher


Introduction
Cell invasion is a regulated process that is physiologically active during embryonic morphogenesis, pregnancy, and wound healing. During cancer progression, deregulated cell invasion processes contribute to many steps of the metastatic dissemination, including cellular escape from primary tumors, intravasation into the blood and lymphatic vascular compartments and metastatic seeding in distant tissues. During this metastatic process, tumor cells undergo an epithelial-to-mesenchymal transition (EMT), a process whereby epithelial cells acquire a phenotype characterized by loss of cell–cell junctions as well as the gain of invasive and migratory properties and the expression of mesenchymal markers. Simultaneously, the endothelium is also altered as local loss of its adherens junctions allows metastatic tumor cells to enter and exit the vascular network at proximity and distance of the primary tumor, respectively. These processes are triggered by microenvironmental factors such as pro-inflammatory cytokines secreted by locally activated stromal cells, hypoxia, extracellular matrix components, and involve several signaling pathways controlled by protein kinases and microRNAs.


Main objectives
Since our previous studies have identified crucial functions for EG-VEGF, microRNA, CK2, and VE-cadherin in cell invasion process, the main objectives of our project are to pursue the characterization of the molecular and cellular mechanisms activated by these factors under both physiological and pathological conditions and to integrate these observations into a unifying model. As cell invasion relies on the interactions between several cell types, paracrine regulations and cross-talks between signaling pathways will be examined in physiological (human placentation) and pathological contexts (cancer, angiogenesis). EMT and tumor vascularization being targets of major importance in tumors, we will focus our research on these two processes. The emerging technology of heterotypic 3D cell cultures will be developed for these cell signaling studies and for anti-metastatic drug screening. Furthermore, analysis of the potential interest of the aforementioned signaling components as diagnostic and prognostic biomarkers for clinical applications will be investigated in collaboration with the clinicians of the group.