CRO2 - INSERM UMR_S 911 - Head of unit : Dominique LOMBARDO

Center for Research in Oncobiology and Oncopharmacology

Organization chart

CRO2 Project.

Four teams constitute the INSERM UMR_S 911 unit :

1. Microtubules-mitochondria communications : implications in oncopharmacology.
   (D.Braguer)
2. Redox Microenvironment, Cytoskeleton and colorectal tumor progression.
   (H. Kovacic, V. Peyrot)
3. Tumoral progression and experimental immunotherapy.
   (D. Lombardo, J-P. Bernard)
4. Angiogenesis and tumoral microenvironment.
   (L. Ouafik, D. Figarella-Branger)

This represents some 55 academics, 36 technicians, some 31 doc and post-doc students.

The UMR 911 has been created (January 1st 2008) to associate within a unique structure all teams from basic to clinic studies, working on cancer of the Campus Santé Timone in Marseille, including numbers of clinical departments of the Marseille’s hospital (AP-HM).

Consequently basic studies are strengthened by clinical studies and applications performed by associate departments of AP-HM.

These transversal studies are possible due to the multi disciplinary of the CRO2 partners including organ-specialized physicians, pharmacologists, biologists and biophysicists. CRO2 plays a key-role in student formation and teaching, it also develop core-facilities such as imaging with the acquisition of an intravital microscope, a confocal microscope and electronic one, video-microscopes and living animal imaging device.

Furthermore CRO2 develops the Timone proteomic core facility (IBISA label) with a Shimazu partnership. These facilities are open to research structures of the area. Thus the CRO2 goal is to participate in the multi-facing researches in oncology and to provide researchers with essential equipment.

Despite recent advances in cancer therapies, its frequency increases. The tumor should be considered as an integrated system constituted with tumor cells, cancer stem cells (or progenitors), stroma cells and vessel cells.

Within the tumor mass cells self-interacts or interacts with their microenvironment which involves the microtubule cytoskeleton, adhesion molecules, the redox state of the microenvironment and necessitates the recruitment of new vessels and the expression of factors impacting the immune system to finally lead to the formation of metastases.

These phenomena and afferent signaling pathways are impacted during cancerogenesis. Many of those aspects in cancerology will be investigated by the teams in CRO2.

The recruitment of new vessels or neo-angiogenesis is essential for the tumor growth bringing nutriments and oxygen.

Hypoxia plays a major role in driving angiogenesis and promoting tumorigenic capacity of cancer stem cell. The microenvironment and hypoxia may also maintain the phenotype of cancer stem cells (which are responsible for relapses) as hypoxia inhibits the neural stem cells differentiation and evokes self-renewal of embryonic cells.

Microtubule cytoskeleton is now considered as an integrator of cell signaling that plays an important role in cell proliferation and cell invasion. It is a major target of anticancer drugs which act by triggering mitochondrial signaling cascade, likely through induction of a cross-talk between microtubules and mitochondria.

The extracellular redox homeostasia and the cell/microenvironment interactions modify cytoskeleton functions. Solid tumors with the evasion to treatment lead to the formation of metastases after a first growing phase and local invasiveness. Metastases formation is a multi steps mechanism with the lost of homotypic cell contacts, the release via the neovasculature of tumor cells from the primary tumor.

These released cells reach and survive in the main circulation to adhere to the vascular endothelium followed by the cell extravasation and the metastasis growth in the target tissue once again involving the micro-environment. The adhesion of neoplastic cells to the endothelium to generate metastases needs the formation of a pre-metastatic niche involving various blood elements (platelets, microparticles…), the need for this niche is likely responsible of the pro-thrombotic state of so many cancer-afflicted patients.

The projects of the UMR911 unit will be devoted to characterize predictive biomarkers of the efficacy of antitumor therapies, to characterize new target for antitumor therapies for the treatment of aggressive and/or frequent solid tumors (pancreas, glioblastoma, neuroblastoma, colon), and to avoid secondary pathologies and to treat side effects (thrombo-embolic diseases, neuropathies..) and metastases.