A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression
| Autor: | Luca Genovese, Andrea Cerutti, Maurilio Ponzoni, Cristina Scielzo, Sabrina Bascones Gleave, Claudia de Lalla, Edoardo Migliori, Linda Pattini, Lydia Scarfò, Laura Mauri, Dejan Lazarevic, Blanca Gonzalez-Farre, Elisa Lenti, Maria Grazia Ciampa, Paolo Ghia, Rosa Bernardi, Monika Wozińska, Nicolò Sacchetti, Diego Farinello, Lucia Bongiovanni, Federico Caligaris-Cappio, Elias Campo, Roberta Valsecchi, David Lligé, Maria Teresa Sabrina Bertilaccio, Silvia Bianchessi, Alessia di Lillo, Andrea Brendolan |
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| Přispěvatelé: | Farinello, Diego, Wozińska, Monika, Lenti, Elisa, Genovese, Luca, Bianchessi, Silvia, Migliori, Edoardo, Sacchetti, Nicolò, Di Lillo, Alessia, Bertilaccio, Maria Teresa Sabrina, De Lalla, Claudia, Valsecchi, Roberta, Gleave, Sabrina Bascone, Lligé, David, Scielzo, Cristina, Mauri, Laura, Ciampa, Maria Grazia, Scarfò, Lydia, Bernardi, Rosa, Lazarevic, Dejan, Gonzalez-Farre, Blanca, Bongiovanni, Lucia, Campo, Elia, Cerutti, Andrea, Ponzoni, Maurilio, Pattini, Linda, Caligaris-Cappio, Federico, Ghia, Paolo, Brendolan, Andrea |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Chemokine Limfomes Chronic lymphocytic leukemia Retinoic acid General Physics and Astronomy chemistry.chemical_compound Citoquines Tumor Microenvironment lcsh:Science Coculture Technique Multidisciplinary biology Chemistry (all) Gene Expression Regulation Neoplastic Leukemia Chemokine secretion Disease Progression Cytokines Female Survival Analysi Signal Transduction Stromal cell Science Tretinoin General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences Physics and Astronomy (all) Retinoids medicine Animals Leucèmia limfocítica crònica CXCL13 Tumor microenvironment Retinoides Biochemistry Genetics and Molecular Biology (all) Animal Stromal Cell General Chemistry medicine.disease Chemokine CXCL13 Leukemia Lymphocytic Chronic B-Cell Survival Analysis Coculture Techniques Mice Inbred C57BL 030104 developmental biology chemistry biology.protein Cancer research lcsh:Q Stromal Cells |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname |
| Popis: | In chronic lymphocytic leukemia (CLL), the non-hematopoietic stromal microenvironment plays a critical role in promoting tumor cell recruitment, activation, survival, and expansion. However, the nature of the stromal cells and molecular pathways involved remain largely unknown. Here, we demonstrate that leukemic B lymphocytes induce the activation of retinoid acid synthesis and signaling in the microenvironment. Inhibition of RA-signaling in stromal cells causes deregulation of genes associated with adhesion, tissue organization and chemokine secretion including the B-cell chemokine CXCL13. Notably, reducing retinoic acid precursors from the diet or inhibiting RA-signaling through retinoid-antagonist therapy prolong survival by preventing dissemination of leukemia cells into lymphoid tissues. Furthermore, mouse and human leukemia cells could be distinguished from normal B-cells by their increased expression of Rarγ2 and RXRα, respectively. These findings establish a role for retinoids in murine CLL pathogenesis, and provide new therapeutic strategies to target the microenvironment and to control disease progression. The stromal microenvironment plays a key role in the expansion of chronic lymphocytic leukemia. Here, the authors use the Eµ-TCL1 mouse model to show that leukemic B-cells induce the activation of retinoic acid synthesis in stromal cells of the lymphoid microenvironment, and that impacting on retinoic acid signalling via diet or chemical inhibition prolonged survival by preventing leukemia dissemination and accumulation in lymphoid tissues. |
| Databáze: | OpenAIRE |
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