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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
Author(s) -
Nur Haneen,
Rao Luigia,
Frassanito Maria Antonia,
De Raeve Hendrik,
Ribatti Domenico,
Mfopou Josué Kunjom,
Van Valckenborgh Els,
De Bruyne Elke,
Vacca Angelo,
Vanderkerken Karin,
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Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13092
Subject(s) - angiogenesis , matrigel , cancer research , neovascularization , immunology , endothelial stem cell , natural killer t cell , biology , microbiology and biotechnology , in vitro , t cell , immune system , biochemistry
Summary 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.