TY - JOUR
T1 - Migration of renal carcinoma cells is dependent on protein kinase Cδ via β1 integrin and focal adhesion kinase
AU - Brenner, Walburgis
AU - Greber, Isabelle
AU - Gudejko-Thiel, Justine
AU - Beitz, Silke
AU - Schneider, Elke
AU - Walenta, Stefan
AU - Peters, Kirsten
AU - Unger, Ron
AU - Thüroff, Joachim W.
PY - 2008/5
Y1 - 2008/5
N2 - Migration and adhesion of tumor cells are essential prerequisites for the formation of metastases in malignant diseases. Protein kinase C (PKC) has been shown to regulate cell migration, adhesion and proliferation. In order to identify a connection between PKC isoforms and tumor progression in renal cell carcinoma (RCC), the influence of PKC isoforms on cell migration, adhesion and proliferation and possible influences of the activity of integrins and focal adhesion kinase (FAK) were analyzed in RCC cells. The experiments were performed in the RCC cell line CCF-RC1 after preincubation of the cells with the PKC inhibitors GF109203X, GÖ6976, RO31-8220 and rottlerin. Cell migration and adhesion were assessed through chemotaxis analysis and adhesion to an endothelial monolayer, respectively. Cell proliferation was analysed by a BrdU incorporation assay. The expression and activity of B1 integrins and FAK were analysed by Western blot analysis. GF109203X reduced cell migration to 69%, the activity of β1 integrins to 63% and FAK expression to 82% compared to untreated cells. Rottlerin reduced cell migration in a concentration-dependent manner to 36%, cell proliferation to 81%, expression and activity of β1 integrins to 72 and 79%, and expression and activity of FAK to 56 and 76% of untreated cells, respectively. RO31-8220 also reduced the expression and activity of β1 integrins as well as the expression of FAK to 84, 66 and 66% of untreated cells, respectively. GÖ6976 reduced the expression of FAK to 60% of untreated cells. Cell migration was only slightly reduced by GÖ6976 to 84% of untreated cells, and cell adhesion remained uninfluenced. These findings show a critical role of PKCδ in the regulation of tumor cell migration, which seems to be caused by affecting the expression and activity of β1 integrins and FAK. These results can provide a basis for new strategies in preventing metastases of renal cell carcinoma.
AB - Migration and adhesion of tumor cells are essential prerequisites for the formation of metastases in malignant diseases. Protein kinase C (PKC) has been shown to regulate cell migration, adhesion and proliferation. In order to identify a connection between PKC isoforms and tumor progression in renal cell carcinoma (RCC), the influence of PKC isoforms on cell migration, adhesion and proliferation and possible influences of the activity of integrins and focal adhesion kinase (FAK) were analyzed in RCC cells. The experiments were performed in the RCC cell line CCF-RC1 after preincubation of the cells with the PKC inhibitors GF109203X, GÖ6976, RO31-8220 and rottlerin. Cell migration and adhesion were assessed through chemotaxis analysis and adhesion to an endothelial monolayer, respectively. Cell proliferation was analysed by a BrdU incorporation assay. The expression and activity of B1 integrins and FAK were analysed by Western blot analysis. GF109203X reduced cell migration to 69%, the activity of β1 integrins to 63% and FAK expression to 82% compared to untreated cells. Rottlerin reduced cell migration in a concentration-dependent manner to 36%, cell proliferation to 81%, expression and activity of β1 integrins to 72 and 79%, and expression and activity of FAK to 56 and 76% of untreated cells, respectively. RO31-8220 also reduced the expression and activity of β1 integrins as well as the expression of FAK to 84, 66 and 66% of untreated cells, respectively. GÖ6976 reduced the expression of FAK to 60% of untreated cells. Cell migration was only slightly reduced by GÖ6976 to 84% of untreated cells, and cell adhesion remained uninfluenced. These findings show a critical role of PKCδ in the regulation of tumor cell migration, which seems to be caused by affecting the expression and activity of β1 integrins and FAK. These results can provide a basis for new strategies in preventing metastases of renal cell carcinoma.
KW - Focal adhesion kinase
KW - Integrin
KW - Metastasis
KW - Protein kinase C isoforms
KW - Renal cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=45849101294&partnerID=8YFLogxK
U2 - 10.3892/ijo.32.5.1125
DO - 10.3892/ijo.32.5.1125
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C2 - 18425341
AN - SCOPUS:45849101294
SN - 1019-6439
VL - 32
SP - 1125
EP - 1131
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 5
ER -
