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

Lucia R. Languino, Amrita Singh, Marco Prisco, Gareth J. Inman, Adam Luginbuhl, Joseph M. Curry, Andrew P. South (Lead / Corresponding author)

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    37 Citations (Scopus)
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    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.

    Original languageEnglish
    Pages (from-to)2432-2437
    Number of pages6
    JournalAmerican Journal of Translational Research
    Volume8
    Issue number5
    Early online date15 May 2016
    Publication statusPublished - 30 May 2016

    Keywords

    • Exosomes
    • Squamous cell carcinoma
    • Transforming growth factor-beta
    • Tumor microenvironment

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