CAPTuR – Control of cell Activation in Tumor Progression and Therapeutic Resistance
EA 3842

The team project focuses on oncogenic mechanisms depending on neurotrophins and specific receptors in tumor growth and mechanisms of therapeutic resistance.

The project is developed over 4 complementary topics :

• Endogenous secretion of neuropeptides and interaction of their signaling pathways involved in cell survival
• Interaction with other tumor cell receptors and with autophagy
• Involvement of neurotrophins in therapeutic resistance due to cancer stem cells
• Functions of exosomes in tumor microenvironment associated to mechanisms of therapeutic escape.

These different topics are achieved by developing translational and transdisciplinary research in order to : (i) Identify and evaluate diagnostic and prognostic biomarkers (ii) to contribute in the development of new tools for diagnosis in collaboration with physicists and chemists teams.

Neuropeptides and Tumor Cell Survival : – Endogenous secretion and cell signaling – Autophagy and neurotrophins – Cancer stem cells – Exosomes and tumor microenvironment

Oncology ; Neuropeptides ; Neurotrophins ; exosomes ; Cancer Stem Cells ; Autophagy ; Biomarkers, technological development

Fluorescence linear and inverted microscopes ; Fluorescence binocular loupe ; Immunochemistry automatic device ; Ultracentrifuge ; Classical and Real time PCR ; Chemi-luminescent detection system for western-blotting analysis G-Box ; Colorimetric and fluorescence microplate readers ; In vitro electroporator ; Cell sorting equipment (SdFFF: sedimentation field flow fractionation) ; Stereotaxy equipments ; Experimental tumor model on chorioallantoic membrane (CAM) and tumor xenograft and PDX mice models; Lentivirus transfection and crispR-Cas9 system ; Isolation and analysis of exosomes ; Access to technical BISCEm plateforms : Animal facilities, flow cytometry, FACS, confocal microscopy, Sequencing and transcriptomic analysis ; Development of diagnostic tools ; Technology transfer and valorization through patent applications.

BISCEm – Research Facility for Integrative Biology, Health, Chemistry and Environment

Fields of application: Health ; Health Technology ; SMEs (Small and medium-sized enterprises) focused on oncology and diagnosis

Industrial applications: Development of diagnostic tools ; Technology transfer and valorization through patent applications

Enterprises created since 2005: Oncomedics (2006) ; Carcidiag Biotech (2016)

• National University Partnerships: Poitiers : UMR CNRS 6187, EA 4331 and EA 3805 ; Strasbourg: UMR CNRS 7200, Therapeutic Innovation Laboratory ; Bordeaux : UMR CNRS 5095, IBCG, Neuro-oncology network from Cancéropôle, Grand Sud-Ouest ; Limoges : CRIBL, UMR CNRS 7276 ; XLIM, UMR CNRS 7252 ; IRCER, UMR 7315

• International University Partnerships: University of Castilla de la Mancha, Albacete : Pr Ricardo Sanchez-Prieto ; University of Padova, Dr Giampietro Viola ; ENEA, Rome, Dr Maria Teresa Mancuso
• National Industrial Partnerships: Institut Roche (Boulogne-Billancourt) ; Neuronax (Clermont-Ferrand) ; ALAIR-AVD (Haute-Vienne) ; Oncomedics ; Kamax / Dyameo (Limoges) ; Carcidiag Biotechnologies (Guéret)

Al Akhrass H, Naves T, Vincent F, Magnaudeix A, Durand K, Bertin F, Melloni B, Jauberteau MO, Lalloué F.  “Sortilin limits EGFR signaling by promoting its internalization in lung cancer”. Nature Commun 2017 Oct 30;8(1):1182. (IF 12.124) Abbaci A, Talbot H, Saada S, Gachard N, Abraham J, Jaccard A, Bordessoule D, Fauchais AL, Naves T, Jauberteau MO. “Neurotensin receptor type 2 protects B-cell chronic lymphocytic leukemia cells from apoptosis”. Oncogene 2017 Oct 23 (IF 7.519) Bibes  R, Gobron  S,  Vincent  F,  Mélin  C, Perraud  A, Labrousse  F, Jauberteau MO, Lalloué F. “Oligopeptide from SCO-spondin inhibits tumor angiogenesis in a glioblastoma model”. Oncotarget 2017 Sep 12;8(49):85969-85983. (IF 5.168) Mazouffre C, Perraud A, Geyl S, Blondy S, de la Cruz MA, Jauberteau MO, Mathonnet M, Verdier M. “Dual inhibition of BDNF/TrkB and autophagy: a promising therapeutic approach for colorectal cancer”. J Cell Mol Med 2017 Oct;21(10):2610-2622 (IF 4. 499) Jawhari S, Bessette B, Hombourger S, Durand K, Lacroix A, Labrousse F, Jauberteau MO, Ratinaud MH, Verdier M. “Autophagy and TrkC/NT-3 signaling joined forces boost the hypoxic glioblastoma cell survival”. Carcinogenesis 2017 Jun 1;38(6):592-603 (IF 5.105) Cheray M, Bessette B, Lacroix A, Mélin C, Jawhari S, Pinet S, Deluche E, Clavère P, Durand K, Sanchez-Prieto R, Jauberteau MO, Battu S, Lalloué F. “KLRC3, a Natural Killer receptor gene, is a key factor involved in glioblastoma tumorigenesis and aggressiveness”. J. Cell. Mol. Med 2017, Feb;21(2):244-253.  (IF 4.499) Pinet S, Bessette B, Vedrenne N, Lacroix A, Richard L, Jauberteau MO, Battu S, Lalloué F. “TrkB-containing exosomes promote the transfer of glioblastoma aggressiveness to YKL-40-inactivated glioblastoma cells”.  Oncotarget 2016, 7(31):50349-50364 (IF 6.359) De la Cruz-Morcillo MA, Berger J, Sánchez-Prieto R, Saada S, Naves T, Guillaudeau A, Perraud A, Sindou P, Lacroix A, Descazeaud A, Lalloué F, Jauberteau MO. “p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma”. Oncotarget 2016, 7(23):34480-97 (IF 6.359) Dubanet L, Bentayeb H, Petit B, Olivrie A, Saada S, de la Cruz-Morcillo MA, Lalloué F, Gourin MP, Bordessoule D, Faumont N, Delage-Corre M, Fauchais AL, Jauberteau MO, Troutaud D. “Anti-apoptotic role and clinical relevance of neurotrophins in diffuse large B-cell lymphomas”. Br J Cancer 2015, 113(6):934-44. (5.569) Wilson CM, Naves T, Vincent F, Melloni B, Bonnaud F, Lalloué F, Jauberteau MO. “Sortilin mediates the release and transfer of exosomes in concert with two tyrosine kinase receptors”. J Cell Sci. 2014, 127(Pt 18):3983-97 (IF 5.432) Naves T, Jawhari S, Jauberteau MO, Ratinaud MH, Verdier M. “Autophagy takes place in mutated p53 neuroblastoma cells in response to hypoxia mimetic CoCl2”. Biochem Pharmacol. 2013, 85:1153-61. (IF 4.7) Saada S, Marget P, Fauchais AL, Lise MC, Chemin G, Sindou P, Martel C, Delpy L, Vidal E, Jaccard A, Troutaud D, Lalloué F, Jauberteau MO. “Differential expression of neurotensin and specific receptors, NTSR1 and NTSR2, in normal and malignant human B lymphocytes”. J Immunol, 2012, 189(11):5293-303. (IF 5.78)