Exosome-mediated transfer from the tumor microenvironment increases TGFβ signaling in squamous cell carcinoma

Languino, L. R., Singh, A., Prisco, M., Inman, G. J. , Luginbuhl, A., Curry, J. M. and South, A. P. (2016) Exosome-mediated transfer from the tumor microenvironment increases TGFβ signaling in squamous cell carcinoma. American Journal of Translational Research, 8(5), pp. 2432-2437. (PMID:27347352) (PMCID:PMC4891457)

Abstract

Transforming growth factor-beta (TGFβ) signaling in cancer is context dependent and acts either as a tumor suppressor or a tumor promoter. Loss of function mutation in TGFβ type II receptor (TβRII) is a frequent event in oral cavity squamous cell carcinoma (SCC). Recently, heterogeneity of TGFβ response has been described at the leading edge of SCC and this heterogeneity has been shown to influence stem cell renewal and drug resistance. Because exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways we investigated whether exosomes contain components of the TGFβ signaling pathway and whether exosome transfer between stromal fibroblasts and tumor cells can influence TGFβ signaling in SCC. We demonstrate that exosomes purified from stromal fibroblasts isolated from patients with oral SCC contains TβRII. We also demonstrate that transfer of fibroblast exosomes increases TGFβ signaling in SCC keratinocytes devoid of TβRII which remain non-responsive to TGFβ ligand in the absence of exosome transfer. Overall our data show that stromal communication with tumor cells can direct TGFβ signaling in SCC.

• Item Type: Articles
• Additional Information: This work was funded in part by: the Dystrophic Epidermolysis Bullosa Research Association (G.J.I. and A.P.S.), a Sidney Kimmel Cancer Center Gold Goal Line Award (A.P.S and J.M.C.), and National Institutes of Health Grants P01CA140043 and R01CA089720 (to L.R.L.).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Inman, Professor Gareth
• Authors: Languino, L. R., Singh, A., Prisco, M., Inman, G. J., Luginbuhl, A., Curry, J. M., and South, A. P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: American Journal of Translational Research
• Publisher: e-Century Publishing Corporation
• ISSN: 1943-8141
• ISSN (Online): 1943-8141
• Published Online: 15 May 2016