Journal
BIOMOLECULES
Volume 11, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/biom11020285
Keywords
prion; Treg cells; lung cancer; ME7; Prnp(0/0); Tga20
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2016R1D1A1B01011371]
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The cellular prion protein PrPC plays a critical role in cancer cell invasion and metastasis by inducing the production of Treg cells and increasing the expression of TGF-beta and PD-L1.
The cellular prion protein (PrPC) is a cell surface glycoprotein expressed in many cell types that plays an important role in normal cellular processes. However, an increase in PrPC expression has been associated with a variety of human cancers, where it may be involved in resistance to the proliferation and metastasis of cancer cells. PrP-deficient (Prnp(0/0)) and PrP-overexpressing (Tga20) mice were studied to evaluate the role of PrPC in the invasion and metastasis of cancer. Tga20 mice, with increased PrPC, died more quickly from lung cancer than did the Prnp(0/0) mice, and this effect was associated with increased transforming growth factor-beta (TGF-beta) and programmed death ligand-1 (PD-L1), which are important for the development and function of regulatory T (Treg) cells. The number of FoxP3(+)CD25(+) Treg cells was increased in Tga20 mice compared to Prnp(0/0) mice, but there was no significant difference in either natural killer or cytotoxic T cell numbers. In addition, mice infected with the ME7 scrapie strain had decreased numbers of Treg cells and decreased expression of TGF-beta and PD-L1. These results suggest that PrPC plays an important role in invasion and metastasis of cancer cells by inducing Treg cells through upregulation of TGF-beta and PD-L1 expression.
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