Webber, J. P. ORCID: https://orcid.org/0000-0003-4772-3014, Spary, L. K., Sanders, A. J. ORCID: https://orcid.org/0000-0002-7997-5286, Chowdhury, R., Jiang, W. G. ORCID: https://orcid.org/0000-0002-3283-1111, Steadman, R. ORCID: https://orcid.org/0000-0002-1303-2496, Wymant, J., Jones, A. T. ORCID: https://orcid.org/0000-0003-2781-8905, Kynaston, H. ORCID: https://orcid.org/0000-0003-1902-9930, Mason, M. D. ORCID: https://orcid.org/0000-0003-1505-2869, Tabi, Z. and Clayton, A. ORCID: https://orcid.org/0000-0002-3087-9226 2015. Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes. Oncogene 34 (3) , pp. 290-302. 10.1038/onc.2013.560 |
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Abstract
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 |
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Date Type: | Publication |
Status: | Published |
Schools: | Pharmacy Medicine |
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: | 07 Nov 2024 21:15 |
URI: | https://orca.cardiff.ac.uk/id/eprint/57143 |
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