Stimulation of invariant natural killer T cells by α-Galactosylceramide activates the JAK-STAT pathway in endothelial cells and reduces angiogenesis in the 5T33 multiple myeloma model

Haneen Nur, Luigia Rao, Maria Antonia Frassanito, Hendrik De Raeve, Domenico Ribatti, Josué Kunjom Mfopou, Els Van Valckenborgh, Elke De Bruyne, Angelo Vacca, Karin Vanderkerken, Eline Menu

Research output: Contribution to journalArticle

Abstract

Tumour pathogenesis in multiple myeloma (MM) correlates with a high vascular index. Therefore, targeting angiogenesis is an important therapeutic tool to reduce MM progression. This study aimed to investigate the role of invariant natural killer T (iNKT) cells in angiogenesis and the mechanisms behind the stimulation by α-Galactosylceramide (α-GalCer). We have previously found that α-GalCer could increase the survival of 5T33MM mice and here we demonstrate that α-GalCer reduces the microvessel density. We performed both in vivo and in vitro angiogenic assays to confirm this observation. We found that conditioned medium of α-GalCer stimulated iNKT cells reduced neovascularization in the chick chorioallantoic membrane and in matrigel plug assays. Moreover, we observed a reduction in proliferation, migration and network formation and an induction of apoptosis upon exposure of murine endothelial cell lines to this conditioned medium. We furthermore observed that the JAK-STAT signaling pathway was highly activated in endothelial cells in response to stimulated iNKT cells, indicating the possible role of IFN-γ in the anti-angiogenic process. In conclusion, these results highlight the possibility of recruiting iNKT cells to target MM and angiogenesis. This gives a rationale for combining immunotherapy with conventional anti-tumour treatments in view of increasing their therapeutic potential.

Original languageEnglish
Pages (from-to)651-663
Number of pages13
JournalBritish Journal of Haematology
Volume167
Issue number5
DOIs
Publication statusPublished - Dec 1 2014

Keywords

  • Invariant natural killer T cells
  • JAK-STAT pathway
  • MM-induced angiogenesis
  • Multiple myeloma
  • α-Galactosylceramide

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Stimulation of invariant natural killer T cells by α-Galactosylceramide activates the JAK-STAT pathway in endothelial cells and reduces angiogenesis in the 5T33 multiple myeloma model'. Together they form a unique fingerprint.

  • Cite this

    Nur, H., Rao, L., Frassanito, M. A., De Raeve, H., Ribatti, D., Mfopou, J. K., Van Valckenborgh, E., De Bruyne, E., Vacca, A., Vanderkerken, K., & Menu, E. (2014). Stimulation of invariant natural killer T cells by α-Galactosylceramide activates the JAK-STAT pathway in endothelial cells and reduces angiogenesis in the 5T33 multiple myeloma model. British Journal of Haematology, 167(5), 651-663. https://doi.org/10.1111/bjh.13092