Involvement of Cellular Prion Protein in Invasion and Metastasis of Lung Cancer by Inducing Treg Cell Development

The cellular prion protein (PrP(C)) is a cell surface glycoprotein expressed in many cell types that plays an important role in normal cellular processes. However, an increase in PrP(C) 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 PrP(C) in the invasion and metastasis of cancer. Tga20 mice, with increased PrP(C), 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-β) 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-β and PD-L1. These results suggest that PrP(C) plays an important role in invasion and metastasis of cancer cells by inducing Treg cells through upregulation of TGF-β and PD-L1 expression.