Changes in the secretory profile of NSCLC-associated fibroblasts after ablative radiotherapy: potential impact on angiogenesis and tumor growth

Hellevik, T., Pettersen, I., Berg, V., Bruun, J., Bartnes, K., Busund, T.-L., Chalmers, A. , Bremnes,, R. and Martinez-Zubiaurre, I. (2013) Changes in the secretory profile of NSCLC-associated fibroblasts after ablative radiotherapy: potential impact on angiogenesis and tumor growth. Translational Oncology, 6(1), pp. 66-74. (doi: 10.1593/tlo.12349) (PMID:23418618) (PMCID:PMC3573655)

[img]
Preview
Text
80986.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

1MB

Abstract

In the context of radiotherapy, collateral effects of ablative ionizing radiation (AIR) on stromal components of tumors remains understudied. In this work, cancer-associated fibroblasts (CAFs) isolated from freshly resected human lung tumors were exposed to AIR (1x18Gy) and analyzed for their release of paracrine factors. Inflammatory mediators and regulators of angiogenesis and tumor growth were analyzed by multiplex protein assays in conditioned medium (CM) from irradiated and non-irradiated CAFs. Additionally, the profile of secreted proteins was examined by proteomics. In functional assays, effects of CAF-CM on proliferative and migratory capacity of lung tumor cells (H-520/H-522) and endothelial cells (HUVECs), and on the tube-forming capacity of endothelial cells was assessed. Our data show that exposure of CAFs to ablative doses of ionizing radiation results in a) down-regulated release of angiogenic factors SDF-1, angiopoietin and thrombospondin-2; b) up-regulated release of growth factor bFGF from most donors, and c) unaffected expression-levels of HGF and inflammatory mediators IL-6, IL-8, IL-1ƒÒ and TNF-£. Conditioned medium from irradiated and control CAFs did not affect differently the proliferative or migratory capacity of tumor cells (H-520/H-522), whereas migratory capacity of endothelial HUVEC cells was partially reduced in the presence of irradiated CAF conditioned medium. Overall we conclude that AIR mediates a transformation on the secretory profile of CAFs that could influence the behavior of other cells in the tumor tissue and hence guide to some extent therapeutic outcomes. The downstream consequences of the changes observed in this study merits further investigations.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Chalmers, Professor Anthony
Authors: Hellevik, T., Pettersen, I., Berg, V., Bruun, J., Bartnes, K., Busund, T.-L., Chalmers, A., Bremnes,, R., and Martinez-Zubiaurre, I.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Translational Oncology
Publisher:Neoplasia Press
ISSN:1944-7124
ISSN (Online):1936-5233
Copyright Holders:Copyright © 2013 Neoplasia Press
First Published:First published in Translational Onocology 6(1):66-74
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record