Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo

Paola Storti, Valentina Marchica, Irma Airoldi, G. Donofrio, Elena Fiorini, Valentina Ferri, D. Guasco, Katia Todoerti, R. Silbermann, J. Anderson, W. Zhao, Luca Agnelli, Marina Bolzoni, Eugenia Martella, Cristina Mancini, Nicoletta Campanini, Douglas M Noonan, P. G. Petronini, Antonino Neri, Franco AversaG. D. Roodman, Nicola Giuliani

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalLeukemia
DOIs
Publication statusAccepted/In press - Jun 17 2016

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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    Storti, P., Marchica, V., Airoldi, I., Donofrio, G., Fiorini, E., Ferri, V., Guasco, D., Todoerti, K., Silbermann, R., Anderson, J., Zhao, W., Agnelli, L., Bolzoni, M., Martella, E., Mancini, C., Campanini, N., Noonan, D. M., Petronini, P. G., Neri, A., ... Giuliani, N. (Accepted/In press). Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo. Leukemia. https://doi.org/10.1038/leu.2016.137