Back to Search
Start Over
Accelerated tumour metastasis due to interferon-γ receptor-mediated dissociation of perivascular cells from blood vessels.
- Source :
-
The Journal of pathology [J Pathol] 2017 Jul; Vol. 242 (3), pp. 334-346. Date of Electronic Publication: 2017 May 25. - Publication Year :
- 2017
-
Abstract
- Angiostasis mediated by interferon (IFN)-γ is a key mechanism of anti-tumour immunity; however, the effect of IFN-γ on host vascular endothelial growth factor A (VEGFA)-expressing cells during tumour progression is still elusive. Here, we developed transgenic mice with IFN-γ receptor (IFNγR) expression under control of the Vegfa promoter (V-γR). In these mice, the IFN-γ responsiveness of VEGFA-expressing cells led to dramatic growth suppression of transplanted lung carcinoma cells. Surprisingly, increased mortality and tumour metastasis were observed in the tumour-bearing V-γR mice, in comparison with the control wild-type and IFNγR-deficient mice. Further study showed that perivascular cells were VEGFA-expressing cells and potential IFN-γ targets. In vivo, tumour vascular perfusion and pericyte association with blood vessels were massively disrupted in V-γR mice. In vitro, IFN-γ inhibited transforming growth factor-β signalling by upregulating SMAD7, and therefore downregulated N-cadherin expression in pericytes. Importantly, IFN-γ neutralization in vivo with a monoclonal antibody reduced tumour metastasis. Together, the results suggest that IFNγR-mediated dissociation of perivascular cells from blood vessels contributes to the acceleration of tumour metastasis. Thus, the inhibition of tumour growth via IFN-γ-induced angiostasis might also accelerate tumour metastasis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<br /> (Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
- Subjects :
- Animals
Cadherins metabolism
Cell Line, Tumor
Down-Regulation
Fibroblasts metabolism
Interferon-gamma metabolism
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Neoplasm Metastasis
Neoplasm Transplantation
Neovascularization, Pathologic metabolism
Neovascularization, Pathologic physiopathology
Pericytes metabolism
Receptors, Interferon deficiency
Receptors, Interferon metabolism
Smad7 Protein physiology
Transforming Growth Factor beta antagonists & inhibitors
Up-Regulation physiology
Vascular Endothelial Growth Factor A metabolism
Interferon gamma Receptor
Lung Neoplasms physiopathology
Receptors, Interferon physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9896
- Volume :
- 242
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 28418194
- Full Text :
- https://doi.org/10.1002/path.4907