Conclusions
Our results indicate that PKC potentiates tumor metastasis to the bone by potentiating translation increase and can be putatively inhibited by pharmacological inhibition.
Material and methods
The effect of the PKC inhibitor Go6983 on epithelial and mesenchymal cell marker expression in the osteosarcoma cell line DAN was determined by immunoblot and immunofluorescence analysis. The in vivo effect of Go6983 was evaluated with a xenograft model using DAN cells.
Methods
The effect of the PKC inhibitor Go6983 on epithelial and mesenchymal cell marker expression in the osteosarcoma cell line DAN was determined by immunoblot and immunofluorescence analysis. The in vivo effect of Go6983 was evaluated with a xenograft model using DAN cells.
Results
Treatment with transforming growth factor β (TGF-β) led to loss of the epithelial cell marker and gain of mesenchymal cell markers in the osteosarcoma cell line, DAN. This transition occurred concomitantly with PKC activation. TGF-β-mediated PKC activation resulted in activation of ribosomal protein 6 (S6), but not S6K1. Pharmacological inhibition of PKC activation attenuated these effects. In a xenograft model of experimental metastasis, pharmacological inhibition of PKC activation over a period of 4 weeks reduced both tumor burden and metastasis to lungs. Conclusions: Our results indicate that PKC potentiates tumor metastasis to the bone by potentiating translation increase and can be putatively inhibited by pharmacological inhibition.