Angiogenesis is critical in the progression of
prostate cancer. However, the interplay between the proliferation kinetics of
tumor endothelial cells (angiogenesis) and
tumor cells has not been investigated. Also,
protein kinase C (PKC) regulates various aspects of
tumor cell growth, but its role in
prostate cancer has not been investigated in detail. Here, we found that the proliferation rates of endothelial and
tumor cells oscillate asynchronously during the growth of human
prostate cancer xenografts. Furthermore, our analyses suggest that PKCbetaII was activated during increased angiogenesis and that PKCbetaII plays a key role in the proliferation of endothelial cells and
tumor cells in human
prostate cancer; treatment with a PKCbetaII-selective inhibitor, betaIIV5-3, reduced angiogenesis and
tumor cell proliferation. We also find a unique effect of PKCbetaII inhibition on normalizing
pericentrin (a
protein regulating cytokinesis), especially in endothelial cells as well as in
tumor cells. PKCbetaII inhibition reduced the level and mislocalization of
pericentrin and normalized microtubule organization in the
tumor endothelial cells. Although
pericentrin has been known to be up-regulated in epithelial cells of
prostate cancers, its level in
tumor endothelium has not been studied in detail. We found that
pericentrin is up-regulated in human
tumor endothelium compared with endothelium adjacent to normal glands in tissues from
prostate cancer patients. Our results suggest that a PKCbetaII inhibitor such as betaIIV5-3 may be used to reduce
prostate cancer growth by targeting both angiogenesis and
tumor cell growth.