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

TY - JOUR

T1 - Exosome-mediated transfer from the tumor microenvironment increases TGFβ signaling in squamous cell carcinoma

AU - Languino, Lucia R.

AU - Singh, Amrita

AU - Prisco, Marco

AU - Inman, Gareth J.

AU - Luginbuhl, Adam

AU - Curry, Joseph M.

AU - South, Andrew P.

PY - 2016/5/30

Y1 - 2016/5/30

N2 - 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.

AB - 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.

KW - Exosomes

KW - Squamous cell carcinoma

KW - Transforming growth factor-beta

KW - Tumor microenvironment

UR - https://www.scopus.com/pages/publications/84971657547

UR - http://www.ajtr.org/V8_No5.html

M3 - Article

AN - SCOPUS:84971657547

VL - 8

SP - 2432

EP - 2437

JO - American Journal of Translational Research

JF - American Journal of Translational Research

IS - 5

ER -