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

doi:10.1038/leu.2016.137

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. AversaG. D. Roodman, N. Giuliani

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2351-2363
Number of pages	13
Journal	Leukemia
Volume	30
Issue number	12
DOIs	https://doi.org/10.1038/leu.2016.137
State	Published - Dec 1 2016
Externally published	Yes

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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Storti, P., Marchica, V., Airoldi, I., Donofrio, G., Fiorini, E., Ferri, V., Guasco, D., Todoerti, K., Silbermann, R., Anderson, J. L., Zhao, W., Agnelli, L., Bolzoni, M., Martella, E., Mancini, C., Campanini, N., Noonan, D. M., Petronini, P. G., Neri, A., ... Giuliani, N. (2016). Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo. Leukemia, 30(12), 2351-2363. https://doi.org/10.1038/leu.2016.137

Storti, P, Marchica, V, Airoldi, I, Donofrio, G, Fiorini, E, Ferri, V, Guasco, D, Todoerti, K, Silbermann, R, Anderson, JL, Zhao, W, Agnelli, L, Bolzoni, M, Martella, E, Mancini, C, Campanini, N, Noonan, DM, Petronini, PG, Neri, A, Aversa, F, Roodman, GD & Giuliani, N 2016, 'Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo', Leukemia, vol. 30, no. 12, pp. 2351-2363. https://doi.org/10.1038/leu.2016.137

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

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.",

author = "P. Storti and V. Marchica and I. Airoldi and G. Donofrio and E. Fiorini and V. Ferri and D. Guasco and K. Todoerti and R. Silbermann and Anderson, {J. L.} and W. Zhao and L. Agnelli and M. Bolzoni and E. Martella and C. Mancini and N. Campanini and Noonan, {D. M.} and Petronini, {P. G.} and A. Neri and F. Aversa and Roodman, {G. D.} and N. Giuliani",

year = "2016",

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doi = "10.1038/leu.2016.137",

language = "English (US)",

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T1 - Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo

AU - Storti, P.

AU - Marchica, V.

AU - Airoldi, I.

AU - Donofrio, G.

AU - Fiorini, E.

AU - Ferri, V.

AU - Guasco, D.

AU - Todoerti, K.

AU - Silbermann, R.

AU - Anderson, J. L.

AU - Zhao, W.

AU - Agnelli, L.

AU - Bolzoni, M.

AU - Martella, E.

AU - Mancini, C.

AU - Campanini, N.

AU - Noonan, D. M.

AU - Petronini, P. G.

AU - Neri, A.

AU - Aversa, F.

AU - Roodman, G. D.

AU - Giuliani, N.

PY - 2016/12/1

Y1 - 2016/12/1

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.

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.

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ER -

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

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