Open AccessEndothelial Interleukin‐6 Defines the Tumorigenic Potential of Primary Human Cancer Stem Cells
Author(s) -
Krishnamurthy Sudha,
Warner Kristy A.,
Dong Zhihong,
Imai Atsushi,
Nör Carolina,
Ward Brent B.,
Helman Joseph I.,
Taichman Russell S.,
Bellile Emily L.,
McCauley Laurie K.,
Polverini Peter J.,
Prince Mark E.,
Wicha Max S.,
Nör Jacques E.
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1793
Subject(s) - biology , cancer stem cell , stromal cell , cancer research , stem cell , endothelial stem cell , immunology , tumor microenvironment , microbiology and biotechnology , in vitro , tumor cells , biochemistry
Head and neck squamous cell carcinomas (HNSCC) contain a small subpopulation of stem cells endowed with unique capacity to generate tumors. These cancer stem cells (CSC) are localized in perivascular niches and rely on crosstalk with endothelial cells for survival and self‐renewal, but the mechanisms involved are unknown. Here, we report that stromal interleukin (IL)−6 defines the tumorigenic capacity of CSC sorted from primary human HNSCC and transplanted into mice. In search for the cellular source of Interleukin‐6 (IL‐6), we observed a direct correlation between IL‐6 levels in tumor‐associated endothelial cells and the tumorigenicity of CSC. In vitro, endothelial cell‐IL‐6 enhanced orosphere formation, p‐STAT3 activation, survival, and self‐renewal of human CSC. Notably, a humanized anti‐IL‐6R antibody (tocilizumab) inhibited primary human CSC‐mediated tumor initiation. Collectively, these data demonstrate that endothelial cell‐secreted IL‐6 defines the tumorigenic potential of CSC, and suggest that HNSCC patients might benefit from therapeutic inhibition of IL‐6/IL‐6R signaling. S tem C ells 2014;32:2845–2857