title: Exosome-mediated transfer from the tumor microenvironment increases TGFβ signaling in squamous cell carcinoma.
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.
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University Philadelphia, USA.
authors.forename: Lucia R
authors.initials: LR
authors.lastname: Languino
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University Philadelphia, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Dermatology & Cutaneous Biology, Thomas Jefferson University Philadelphia, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Prisco
authors.affiliation: Division of Cancer Research, School of Medicine, University of Dundee UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Inman
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Thomas Jefferson UniversityPhiladelphia, USA; Squamous Cell Carcinoma Tumor Ecology and Microenvironment (STEM) Research Group, Thomas Jefferson UniversityPhiladelphia, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Luginbuhl
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Thomas Jefferson UniversityPhiladelphia, USA; Squamous Cell Carcinoma Tumor Ecology and Microenvironment (STEM) Research Group, Thomas Jefferson UniversityPhiladelphia, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Curry
authors.affiliation: Department of Dermatology & Cutaneous Biology, Thomas Jefferson UniversityPhiladelphia, USA; Squamous Cell Carcinoma Tumor Ecology and Microenvironment (STEM) Research Group, Thomas Jefferson UniversityPhiladelphia, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: South
keywords: Exosomes; squamous cell carcinoma; transforming growth factor-beta; tumor microenvironment