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Prion protein ablation increases cellular aggregation and embolization contributing to mechanisms of metastasis
Author(s) -
Muras Angelita G.,
Hajj Glaucia N.M.,
Ribeiro Karina B.,
Nomizo Regina,
ogaki Sueli,
Chammas Roger,
Martins Vilma R.
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24425
Subject(s) - prnp , biology , fibronectin , vitronectin , extracellular matrix , integrin , laminin , cell culture , microbiology and biotechnology , cancer research , cell , biochemistry , gene , allele , genetics
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