Received for publication March 1, 2006.
Revised April 13, 2006.
Accepted for publication April 13, 2006.

PKC Mediates Platelet-Induced Breast Cancer Cell Invasion

Abstract

Background: Platelets play an important role in carcinogenesis, but the underlying molecular mechanisms remain poorly understood. Aim: to investigate the effects of platelets on in vitro invasion of MCF7 human breast cancer cells. Methods: Human MCF7 cells were used to study their interactions with platelets using aggregometry and cell invasion chambers. Zymography and quantitative PCR were used to study matrix metalloproteinases (MMPs), whereas western blot was used to study PKC in MCF7 cells. Results: We observed that platelets promoted invasion of MCF7 cells (3 fold-increase, p<0.05, n=3) and that this process correlated with a dramatic increase in MMP-9 (8 fold-increase, p<0.001, n=3), which is known to facilitate cancer cell invasion. Since both, platelets and MCF7 cells have been shown to release MMP-9, we investigated the cellular source that accounted for this increase. The time-course and the use of specific protein synthesis inhibitors demonstrated that most of the increase in MMP-9 levels derived from de novo synthesis of this protease by cancer cells. Furthermore, platelets activated PKC in MCF7 cells after one hour of incubation (18.45±4.75% increase, p<0.05, n=4-7), which, in turn, led to an upregulation of MMP-9 mRNA (from 60 ± 20 to 1040 ± 100 pg, p<0.001, n=3) and protein levels (18-fold increase, p<0.001, n=3), with the subsequent cell invasion-promoting effects. Conclusion: PKC plays a crucial role in transducing the invasion-promoting effects of platelets in breast cancer cells and the specific inhibition of PKC may be a strategy to decrease platelet-mediated cancer cell invasion.

Key words: TCIPA, breast cancer, cancer cell invasion, matrix metalloproteinases, platelets, protein kinase C