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Elastin MIcrofibriL INterfacer1 (EMILIN-1) is an alternative prosurvival VLA-4 ligand in chronic lymphocytic leukemia.
Tissino, Erika; Pivetta, Eliana; Capuano, Alessandra; Capasso, Guido; Bomben, Riccardo; Caldana, Chiara; Rossi, Francesca Maria; Pozzo, Federico; Benedetti, Dania; Boldorini, Renzo; Gaidano, Gianluca; Rossi, Davide; Zamò, Alberto; Hartmann, Tanja Nicole; Doliana, Roberto; Colombatti, Alfonso; Gattei, Valter; Spessotto, Paola; Zucchetto, Antonella.
Afiliación
  • Tissino E; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Pivetta E; Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Capuano A; Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Capasso G; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Bomben R; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Caldana C; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Rossi FM; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Pozzo F; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Benedetti D; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Boldorini R; Dipartimento di Scienze della Salute, Scuola di Medicina, University of Eastern Piedmont, Novara, Italy.
  • Gaidano G; Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.
  • Rossi D; Department of Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Zamò A; Institute of Pathology, University of Würzburg, Bayern, Germany.
  • Hartmann TN; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Baden-Württemberg, Germany.
  • Doliana R; Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Colombatti A; Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Gattei V; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Spessotto P; Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Zucchetto A; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
Hematol Oncol ; 40(2): 181-190, 2022 Apr.
Article en En | MEDLINE | ID: mdl-34783040
CD49d, the α4 chain of the VLA-4 integrin, is a negative prognosticator in chronic lymphocytic leukemia (CLL) with a key role in CLL cell-microenvironment interactions mainly occurring via its ligands VCAM-1 and fibronectin. In the present study, we focused on EMILIN-1 (Elastin-MIcrofibriL-INterfacer-1), an alternative VLA-4 ligand whose role has been so far reported only in non-hematological settings, by investigating: i) the distribution of EMILIN-1 in CLL-involved tissues; ii) the capability of EMILIN-1 to operate, via its globular C1q (gC1q) domain, as additional adhesion ligand in CLL; iii) the functional meaning of EMILIN-1 gC1q/VLA-4 interactions in CLL. EMILIN-1 is widely present in the CLL-involved areas of bone marrow biopsies (BMBs) without difference between CD49d negative and positive cases, displaying at least three different expression patterns: "fibrillar", "dot-like" and "mixed". The lack in CLL-BMB of neutrophil elastase, whose proteolytic activity degrades EMILIN-1 and impairs EMILIN-1 function, suggests full functional EMILIN-1 in CLL independently of its expression pattern. Functionally, EMILIN-1 gC1q domain promotes adhesion of CLL cells through specific interaction with VLA-4, and releases pro-survival signals for CLL cells, as demonstrated by enhanced ERK and AKT phosphorylation and impairment of in-vitro-induced apoptosis. EMILIN-1/VLA-4 interaction can efficiently contribute to the maintenance of the neoplastic clone in CLL.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B Límite: Humans Idioma: En Revista: Hematol Oncol Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B Límite: Humans Idioma: En Revista: Hematol Oncol Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido