Galectin-1 (Gal-1) is involved in tumoral angiogenesis, hypoxia and metastases. Actually the Gal-1 expression profile in multiple myeloma (MM) patients and its pathophysiological role in MM-induced angiogenesis and tumoral growth are unknown. In this study, we found that Gal-1 expression by MM cells was upregulated in hypoxic conditions and that stable knockdown of hypoxia inducible factor-1α significantly downregulated its expression. Therefore, we performed Gal-1 inhibition using lentivirus transfection of shRNA anti-Gal-1 in human myeloma cell lines (HMCLs), and showed that its suppression modified transcriptional profiles in both hypoxic and normoxic conditions. Interestingly, Gal-1 inhibition in MM cells downregulated proangiogenic genes, including MMP9 and CCL2, and upregulated the antiangiogenic ones SEMA3A and CXCL10. Consistently, Gal-1 suppression in MM cells significantly decreased their proangiogenic properties in vitro. This was confirmed in vivo, in two different mouse models injected with HMCLs transfected with anti-Gal-1 shRNA or the control vector. Gal-1 suppression in both models significantly reduced tumor burden and microvascular density as compared with the control mice. Moreover, Gal-1 suppression induced smaller lytic lesions on X-ray in the intratibial model. Overall, our data indicate that Gal-1 is a new potential therapeutic target in MM blocking angiogenesis.
Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo / P. Storti, V. Marchica, I. Airoldi, G. Donofrio, E. Fiorini, V. Ferri, D. Guasco, K. Todoerti, R. Silbermann, J.L. Anderson, W. Zhao, L. Agnelli, M. Bolzoni, E. Martella, C. Mancini, N. Campanini, D.M. Noonan, P.G. Petronini, A. Neri, F. Aversa, G.D. Roodman, N. Giuliani. - In: LEUKEMIA. - ISSN 0887-6924. - (2016). [Epub ahead of print]
|Titolo:||Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo|
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
|Data di pubblicazione:||2016|
|Data ahead of print / Data di stampa:||17-giu-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/leu.2016.137|
|Appare nelle tipologie:||01 - Articolo su periodico|