Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes

Webber, J. P. ORCID:, Spary, L. K., Sanders, A. J. ORCID:, Chowdhury, R., Jiang, W. G. ORCID:, Steadman, R. ORCID:, Wymant, J., Jones, A. T. ORCID:, Kynaston, H. ORCID:, Mason, M. D. ORCID:, Tabi, Z. and Clayton, A. ORCID: 2015. Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes. Oncogene 34 (3) , pp. 290-302. 10.1038/onc.2013.560

[thumbnail of Webber et al.pdf]
PDF - Accepted Post-Print Version
Download (408kB) | Preview


Activation of myofibroblast rich stroma is a rate-limiting step essential for cancer progression. The responsible factors are not fully understood, but TGFβ1 is probably critical. A proportion of TGFβ1 is associated with extracellular nano-vesicles termed exosomes, secreted by carcinoma cells, and the relative importance of soluble and vesicular TGFβ in stromal activation is presented. Prostate cancer exosomes triggered TGFβ1-dependent fibroblast differentiation, to a distinctive myofibroblast phenotype resembling stromal cells isolated from cancerous prostate tissue; supporting angiogenesis in vitro and accelerating tumour growth in vivo. Myofibroblasts generated using soluble TGFβ1 were not pro-angiogenic or tumour-promoting. Cleaving heparan sulphate side chains from the exosome surface had no impact on TGFβ levels yet attenuated SMAD-dependent signalling and myofibroblastic differentiation. Eliminating exosomes from the cancer cell secretome, targeting Rab27a, abolished differentiation and lead to failure in stroma-assisted tumour growth in vivo. Exosomal TGFβ1 is therefore required for the formation of tumour-promoting stroma.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: exosomes; prostate; stroma; fibroblast; TGFβ
Additional Information: Published online before print 20 Jan 2014.
Publisher: Springer Nature
ISSN: 0950-9232
Funders: Cancer Research UK
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 22 November 2013
Last Modified: 18 Apr 2024 18:26

Citation Data

Cited 288 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics