PMID- 32724091 OWN - NLM STAT- MEDLINE DCOM- 20201211 LR - 20210728 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Jul 28 TI - BDNF belongs to the nurse-like cell secretome and supports survival of B chronic lymphocytic leukemia cells. PG - 12572 LID - 10.1038/s41598-020-69307-1 [doi] LID - 12572 AB - Evading apoptosis and sustained survival signaling pathways are two central hallmarks of B-cell chronic lymphocytic leukemia (B-CLL) cells. In this regard, nurse-like cells (NLC), the monocyte-derived type 2 macrophages, deliver stimulatory signals via B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and the C-X-C Motif Chemokine Ligand 12 (CXCL12). Previously, we demonstrated that brain-derived neurotrophic factor (BDNF) protects B-CLL cells from spontaneous apoptosis by activating the oncogenic complex NTSR2-TrkB (neurotensin receptor 2-tropomyosin-related kinase receptor B), only overexpressed in B-CLL cells, inducing anti-apoptotic protein Bcl-2 (B-cell lymphoma 2) expression and Src kinase survival signaling pathways. Herein, we demonstrate that BDNF belongs to the NLC secretome and promotes B-CLL survival. This was demonstrated in primary B-CLL co-cultured with their autologous NLC, compared to B-CLL cells cultured alone. Inhibition of BDNF in co-cultures, enhances B-CLL apoptosis, whereas its exogenous recombinant activates pro-survival pathways in B-CLL cultured alone (i.e. Src activation and Bcl-2 expression), at a higher level than those obtained by the exogenous recombinant cytokines BAFF, APRIL and CXCL12, the known pro-survival cytokines secreted by NLC. Together, these results showed that BDNF release from NLC trigger B-CLL survival. Blocking BDNF would support research strategies against pro-survival cytokines to limit sustained B-CLL cell survival. FAU - Talbot, Hugo AU - Talbot H AD - Equipe Accueil 3842 CAPTuR, Faculty of Medicine, Limoges University, 2, Rue du Docteur Marcland, 87025, Limoges Cedex, France. FAU - Saada, Sofiane AU - Saada S AD - Equipe Accueil 3842 CAPTuR, Faculty of Medicine, Limoges University, 2, Rue du Docteur Marcland, 87025, Limoges Cedex, France. FAU - Barthout, Elodie AU - Barthout E AD - Equipe Accueil 3842 CAPTuR, Faculty of Medicine, Limoges University, 2, Rue du Docteur Marcland, 87025, Limoges Cedex, France. FAU - Gallet, Paul-Francois AU - Gallet PF AD - Equipe Accueil 3842 CAPTuR, Faculty of Medicine, Limoges University, 2, Rue du Docteur Marcland, 87025, Limoges Cedex, France. FAU - Gachard, Nathalie AU - Gachard N AD - Hematology Laboratory, Dupuytren Hospital University Center of Limoges, Limoges Cedex, France. AD - CNRS-UMR 7276, Limoges University, Limoges Cedex, France. FAU - Abraham, Julie AU - Abraham J AD - CNRS-UMR 7276, Limoges University, Limoges Cedex, France. AD - Department of Hematology, Dupuytren Hospital University Center of Limoges, Limoges Cedex, France. FAU - Jaccard, Arnaud AU - Jaccard A AD - CNRS-UMR 7276, Limoges University, Limoges Cedex, France. AD - Department of Hematology, Dupuytren Hospital University Center of Limoges, Limoges Cedex, France. FAU - Troutaud, Danielle AU - Troutaud D AD - Equipe Accueil 3842 CAPTuR, Faculty of Medicine, Limoges University, 2, Rue du Docteur Marcland, 87025, Limoges Cedex, France. FAU - Lalloue, Fabrice AU - Lalloue F AD - Equipe Accueil 3842 CAPTuR, Faculty of Medicine, Limoges University, 2, Rue du Docteur Marcland, 87025, Limoges Cedex, France. FAU - Naves, Thomas AU - Naves T AD - Equipe Accueil 3842 CAPTuR, Faculty of Medicine, Limoges University, 2, Rue du Docteur Marcland, 87025, Limoges Cedex, France. FAU - Fauchais, Anne-Laure AU - Fauchais AL AD - Equipe Accueil 3842 CAPTuR, Faculty of Medicine, Limoges University, 2, Rue du Docteur Marcland, 87025, Limoges Cedex, France. AD - Department of Internal Medicine, Dupuytren Hospital University Center of Limoges, Limoges Cedex, France. FAU - Jauberteau, Marie-Odile AU - Jauberteau MO AD - Equipe Accueil 3842 CAPTuR, Faculty of Medicine, Limoges University, 2, Rue du Docteur Marcland, 87025, Limoges Cedex, France. m-o.jauberteau-marchan@unilim.fr. AD - Department of Immunology, Dupuytren Hospital University Center of Limoges, Limoges Cedex, France. m-o.jauberteau-marchan@unilim.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200728 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (B-Cell Activating Factor) RN - 0 (BCL2 protein, human) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - 0 (NTSR2 protein, human) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Receptors, Neurotensin) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (tropomyosin-related kinase-B, human) SB - IM MH - Apoptosis MH - B-Cell Activating Factor/genetics/metabolism MH - B-Lymphocytes/cytology/metabolism MH - Biological Transport MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Humans MH - Leukemia, Lymphocytic, Chronic, B-Cell/genetics/*metabolism/physiopathology MH - Macrophages/*metabolism MH - Membrane Glycoproteins/genetics/metabolism MH - Monocytes/metabolism MH - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism MH - Receptor, trkB/genetics/metabolism MH - Receptors, Neurotensin/genetics/metabolism MH - Signal Transduction PMC - PMC7387561 COIS- The authors declare no competing interests. EDAT- 2020/07/30 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/07/28 CRDT- 2020/07/30 06:00 PHST- 2019/10/30 00:00 [received] PHST- 2020/06/22 00:00 [accepted] PHST- 2020/07/30 06:00 [entrez] PHST- 2020/07/30 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/07/28 00:00 [pmc-release] AID - 10.1038/s41598-020-69307-1 [pii] AID - 69307 [pii] AID - 10.1038/s41598-020-69307-1 [doi] PST - epublish SO - Sci Rep. 2020 Jul 28;10(1):12572. doi: 10.1038/s41598-020-69307-1.