Abstract
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 (Prnp0/0) 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 Prnp0/0 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 Prnp0/0 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 PrPC plays an important role in invasion and metastasis of cancer cells by inducing Treg cells through upregulation of TGF-β and PD-L1 expression.
Highlights
Received: 18 January 2021The cellular prion protein (PrPC ) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein widely expressed in various tissues but predominantly expressed in the central nervous system
To evaluate the role of PrPC in invasion and metastasis of lung cancer, we intravenously injected B16F10-treated mice (B16F10) melanoma cells into Prnp0/0, Prnp+/+, and Prnp−overexpressing (Tga20)
The Prnp levels at the end-stage of cancer were upregulated in both Prnp+/+ and Tga20 mice (Figure 1C). These results indicate that PrPC expression is associated with survival time and lung cancer development
Summary
Received: 18 January 2021The cellular prion protein (PrPC ) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein widely expressed in various tissues but predominantly expressed in the central nervous system. PrPC has been detected on the surface of lymphocytes in humans and mice [1,2,3] and plays an important role in lymphoid cells and spleen structure formation [4,5,6]. An increase in PrPC expression has been associated with a poor prognosis and reported in a variety of human cancers, including pancreatic cancer, breast cancer, gastric carcinoma, osteosarcoma, and melanoma [18,19,20,21,22]. Studies to elucidate the mechanism have been performed by many groups through silencing or overexpressing PrPC in human cancer cell lines. Gil et al reported that PrPC silencing in MD-MB231 breast cancer cell line led to ERK deactivation and matrix metalloprotease-9
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