TY - JOUR
T1 - Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo
AU - Storti, Paola
AU - Marchica, Valentina
AU - Airoldi, Irma
AU - Donofrio, G.
AU - Fiorini, Elena
AU - Ferri, Valentina
AU - Guasco, D.
AU - Todoerti, Katia
AU - Silbermann, R.
AU - Anderson, J.
AU - Zhao, W.
AU - Agnelli, Luca
AU - Bolzoni, Marina
AU - Martella, Eugenia
AU - Mancini, Cristina
AU - Campanini, Nicoletta
AU - Noonan, Douglas M
AU - Petronini, P. G.
AU - Neri, Antonino
AU - Aversa, Franco
AU - Roodman, G. D.
AU - Giuliani, Nicola
PY - 2016
Y1 - 2016
N2 - 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.Leukemia advance online publication, 17 June 2016; doi:10.1038/leu.2016.137.
AB - 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.Leukemia advance online publication, 17 June 2016; doi:10.1038/leu.2016.137.
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U2 - 10.1038/leu.2016.137
DO - 10.1038/leu.2016.137
M3 - Article
VL - 30
SP - 2351
EP - 2363
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 12
ER -