Prion protein ablation increases cellular aggregation and embolization contributing to mechanisms of metastasis
✍ Scribed by Angelita G. Muras; Glaucia N.M. Hajj; Karina B. Ribeiro; Regina Nomizo; Sueli Nonogaki; Roger Chammas; Vilma R. Martins
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- French
- Weight
- 315 KB
- Volume
- 125
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Cellular Prion Protein (PrP^C^) is a cell surface protein highly expressed in the nervous system, and to a lesser extent in other tissues. PrP^C^ binds to the extracellular matrix laminin and vitronectin, to mediate cell adhesion and differentiation. Herein, we investigate how PrP^C^ expression modulates the aggressiveness of transformed cells. Mesenchymal embryonic cells (MEC) from wild‐type (Prnp^+/+^) and PrP^C^‐null (Prnp^0/0^) mice were immortalized and transformed by co‐expression of ras and myc. These cells presented similar growth rates and tumor formation in vivo. When injected in the tail vein, Prnp^0/0^ras/myc cells exhibited increased lung colonization compared with Prnp^+/+^ras/myc cells. Additionally, Prnp^0/0^ras/myc cells form more aggregates with blood components than Prnp^+/+^ras/myc cells, facilitating the arrest of Prnp^0/0^ras/myc cells in the lung vasculature. Integrin α~v~β~3~ is more expressed and activated in MEC and in transformed Prnp^0/0^ cells than in the respective Prnp^+/+^ cells. The blocking of integrin α~v~β~3~ by RGD peptide reduces lung colonization in transformed Prnp^0/0^ cells to similar levels of those presented by transformed Prnp^+/+^ cells. Our data indicate that PrP^C^ negatively modulates the expression and activation of integrin α~v~β~3~ resulting in a more aggressive phenotype. These results indicate that PrP^C^ may have main implications in modulating metastasis formation. © 2009 UICC