Protein Kinase Cδ Mediates Platelet-Induced Breast Cancer Cell Invasion

Abstract

Platelets play an important role in carcinogenesis, but the underlying molecular mechanisms remain poorly understood. To investigate the effects of platelets on in vitro invasion of MCF7 human breast cancer cells, human MCF7 cells were used to study their interactions with platelets using aggregometry and cell invasion chambers. Zymography and quantitative polymerase chain reaction (PCR) were used to study matrix metalloproteinases (MMPs), whereas Western blot was used to study protein kinase C (PKC) ␦ in MCF7 cells. We observed that platelets promoted invasion of MCF7 cells (3-fold increase, p Ͻ 0.05, n ϭ 3) and that this process correlated with a dramatic increase in MMP-9 (8 fold-increase, p Ͻ 0.001, n ϭ 3), which is known to facilitate cancer cell invasion. Because 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.

Importance of PKCδ signaling in fractionated-radiation-induced expansion of glioma-initiating cells and resistance to cancer treatment

“…PKCs have been implicated in the progression and maintenance of the malignant phenotype of certain cancers, including gliomas, and colon, pancreatic and breast cancers (Alonso-Escolano et al, 2006;Bredel and Pollack, 1997;El-Rayes et al, 2008;Gokmen-Polar et al, 2001;Grossoni et al, 2007). Potentiation of the malignant phenotype might be mediated by activation of selective PKC isoenzymes or through altered expression of the isoenzyme profile compared with the originating tissue (Steinberg, 2004).…”

“…Moreover, there is a substantial body of evidence linking PKC to the initiation and progression of certain types of cancers, including gliomas, and breast, pancreatic and colon cancers (Alonso-Escolano et al, 2006;Bredel and Pollack, 1997;El-Rayes et al, 2008;Gokmen-Polar et al, 2001;Grossoni et al, 2007). Total PKC expression and activity levels are significantly higher in normal brain tissue than in non-brain tissues, suggesting that this serine/threonine kinase has a fundamental role in normal brain physiology (Nelsona and Alkona, 2009;Steinhart et al, 2007).…”

PCPH/ENTPD5 Expression Enhances the Invasiveness of Human Prostate Cancer Cells by a Protein Kinase Cδ–Dependent Mechanism

“…Interestingly, PKCy inactivation by rottlerin, its specific inhibitor, or PKCy down-regulation by siRNA was reported to decrease the migration and invasiveness of DU145 and PC-3 cells provoked by stimulation of the epidermal growth factor pathway (40,41). Although sometimes even contradictory functions have been attributed to PKCy (42)(43)(44), including its function in regulating invasion (45)(46)(47), it seems clear that, as an essential component of a novel (PCPH-PKC-collagen I) pathway through which PCPH regulates the expression of collagen I, PKCy acts as a promoter of invasiveness in prostate carcinoma cells. Whether PKCy also acts as a mediator of the known prosurvival function of PCPH in prostate carcinoma remains to be elucidated.…”

Cellular responses to EGFR inhibitors and their relevance to cancer therapy

“…Other pathways that may also be involved in EGFR-mediated migration and invasion include the MAP kinase and protein kinase C delta (PKC-δ) pathways [48,49]. PKC-δ was shown to be overexpressed in two invasive prostate cell lines relative to normal prostate epithelial cells [50].…”