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Molecular targets for therapy

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

Leukemia volume 30, pages 2351–2363 (2016)Cite this article

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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.

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Acknowledgements

This work was supported in part by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG2014 no. 15531 (to NG) and IG13018 (to IA). This work was also supported by a fellowship Fondazione Italiana per la Ricerca sul Cancro id. 18152 (MB) and two fellowship by ParmAIL (Associazione italiana contro le leucemie-linfomi e myeloma, Parma) (VM and DG). We thank Dirce Gennari for her technical support.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, , Parma, Italy

    P Storti, V Marchica, E Fiorini, V Ferri, D Guasco, M Bolzoni, F Aversa & N Giuliani

  2. 'Laboratorio di Oncologia', Istituto Giannina Gaslini, Genova, Italy

    I Airoldi

  3. Department of Medical-Veterinary Science, University of Parma, Parma, Italy

    G Donofrio

  4. Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy

    V Ferri & D M Noonan

  5. Laboratory of Pre-clinical and Translational Research, IRCCS, Rionero in Vulture, Italy

    K Todoerti

  6. Hematology, Indiana University, Indianapolis, IN, USA

    R Silbermann, J L Anderson, W Zhao & G D Roodman

  7. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    L Agnelli

  8. Pathology, 'Azienda Ospedaliero-Universitaria', Parma, Italy

    E Martella, C Mancini, N Campanini & A Neri

  9. Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy

    P G Petronini

  10. Hematology Unit, 'Fondazione IRCCS Ca' Granda', 'Ospedale Maggiore Policlinico', Milan, Italy

    A Neri

  11. Hematology and BMT Center, CoreLab, 'Azienda Ospedaliero-Universitaria', Parma, Italy

    F Aversa & N Giuliani

  12. Richard L. Roudebush VA Medical Center, , Indianapolis, IN, USA

    G D Roodman

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Correspondence to N Giuliani.

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Storti, P., Marchica, V., Airoldi, I. et al. Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo. Leukemia 30, 2351–2363 (2016). https://doi.org/10.1038/leu.2016.137

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