Prion protein ablation increases cellular aggregation and embolization contributing to mechanisms of metastasis
Angelita G. Muras
Cellular and Molecular Biology Group, Ludwig Institute for Cancer Research, São Paulo, SP, Brazil
Centro de Tratamento e Pesquisa, Hospital A.C. Camargo, São Paulo, SP, Brazil
Search for more papers by this authorGlaucia N.M. Hajj
Cellular and Molecular Biology Group, Ludwig Institute for Cancer Research, São Paulo, SP, Brazil
Search for more papers by this authorKarina B. Ribeiro
Centro de Tratamento e Pesquisa, Hospital A.C. Camargo, São Paulo, SP, Brazil
Search for more papers by this authorRegina Nomizo
Centro de Tratamento e Pesquisa, Hospital A.C. Camargo, São Paulo, SP, Brazil
Search for more papers by this authorRoger Chammas
Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
Search for more papers by this authorCorresponding Author
Vilma R. Martins
Cellular and Molecular Biology Group, Ludwig Institute for Cancer Research, São Paulo, SP, Brazil
Cellular and Molecular Biology Laboratory, Ludwig Institute for Cancer Research, Rua João Julião 245, 1A, Zip Code: 01323-903. São Paulo, SP, BrazilSearch for more papers by this authorAngelita G. Muras
Cellular and Molecular Biology Group, Ludwig Institute for Cancer Research, São Paulo, SP, Brazil
Centro de Tratamento e Pesquisa, Hospital A.C. Camargo, São Paulo, SP, Brazil
Search for more papers by this authorGlaucia N.M. Hajj
Cellular and Molecular Biology Group, Ludwig Institute for Cancer Research, São Paulo, SP, Brazil
Search for more papers by this authorKarina B. Ribeiro
Centro de Tratamento e Pesquisa, Hospital A.C. Camargo, São Paulo, SP, Brazil
Search for more papers by this authorRegina Nomizo
Centro de Tratamento e Pesquisa, Hospital A.C. Camargo, São Paulo, SP, Brazil
Search for more papers by this authorRoger Chammas
Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
Search for more papers by this authorCorresponding Author
Vilma R. Martins
Cellular and Molecular Biology Group, Ludwig Institute for Cancer Research, São Paulo, SP, Brazil
Cellular and Molecular Biology Laboratory, Ludwig Institute for Cancer Research, Rua João Julião 245, 1A, Zip Code: 01323-903. São Paulo, SP, BrazilSearch for more papers by this authorAbstract
Cellular Prion Protein (PrPC) is a cell surface protein highly expressed in the nervous system, and to a lesser extent in other tissues. PrPC binds to the extracellular matrix laminin and vitronectin, to mediate cell adhesion and differentiation. Herein, we investigate how PrPC expression modulates the aggressiveness of transformed cells. Mesenchymal embryonic cells (MEC) from wild-type (Prnp+/+) and PrPC-null (Prnp0/0) 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, Prnp0/0ras/myc cells exhibited increased lung colonization compared with Prnp+/+ras/myc cells. Additionally, Prnp0/0ras/myc cells form more aggregates with blood components than Prnp+/+ras/myc cells, facilitating the arrest of Prnp0/0ras/myc cells in the lung vasculature. Integrin αvβ3 is more expressed and activated in MEC and in transformed Prnp0/0 cells than in the respective Prnp+/+ cells. The blocking of integrin αvβ3 by RGD peptide reduces lung colonization in transformed Prnp0/0 cells to similar levels of those presented by transformed Prnp+/+ cells. Our data indicate that PrPC negatively modulates the expression and activation of integrin αvβ3 resulting in a more aggressive phenotype. These results indicate that PrPC may have main implications in modulating metastasis formation. © 2009 UICC
Supporting Information
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| IJC_24425_sm_SuppFig3.tif8.3 MB | Supporting Information Figure 3. |
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