The progression to prostate cancer - a role for the novel growth-promoting cytokines pleiotrophin (PTN) and midkine (MK) in prostate stromal and epithelial cell proliferation and the regulation of protein kinases B and C

Dr Martin Rumsby, University of York

A major problem in discovering how prostate cancer (PCa) develops is our limited understanding of how normal prostate cells grow. Thus we need to define all the factors which control proliferation in stromal and epithelial compartments of the prostate.

Here we investigate how two novel growth-promoting proteins pleiotrophin (PTN) and midkine (MK) control the proliferation and motility of normal prostate cells and whether their effects become altered in PCa. The roles of PTN/MK in prostate are not widely studied which is surprising since i, in other tissues PTN/MK regulate how epithelial and stromal cells communicate with each other,  ii, concentrations of PTN or MK are raised in many cancer cells and iii, PTN can transform normal cells to a cancer form. Additionally, our research shows that stromal cells from PCa tissue secrete PTN with the potential to alter the growth/developmental properties of neighbouring epithelial cells.

We will characterise how PTN/MK interact with normal prostate stromal and epithelial cells to activate intracellular proteins fundamental to controlling cell growth and motility. Similar experiments on stromal/epithelial cells from PCa tissue and on model normal and tumour-derived epithelial cell lines, will reveal how PTN/MK signalling pathways change as PCa develops. PTN/MK have been suggested as potential targets for cancer therapy. Our results may identify specific PTN/MK signalling pathways in normal and tumorigenic prostate cells that could become potential targets to inhibit the development or progression of PCa. To make any PTN/MK directed therapy available and safe, we must firstly define how they work!

Project commenced
October 2008

Length of project
2 years

Amount Supported
£99,911