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Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts
Laboratory for Molecular Cellular Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna 1090, Austria
Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo N-0310, Norway
* Author to whom correspondence should be addressed.
Received: 8 August 2013; in revised form: 22 August 2013 / Accepted: 26 August 2013 / Published: 3 September 2013
Abstract: The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF). PlGF is a member of the vascular endothelial growth factor (VEGF) family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.
Keywords: prostate cancer; placental growth factor; xenograft model; tumor-host interaction; tumor angiogenesis
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Zins, K.; Thomas, A.; Lucas, T.; Sioud, M.; Aharinejad, S.; Abraham, D. Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts. Int. J. Mol. Sci. 2013, 14, 17958-17971.
Zins K, Thomas A, Lucas T, Sioud M, Aharinejad S, Abraham D. Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts. International Journal of Molecular Sciences. 2013; 14(9):17958-17971.
Zins, Karin; Thomas, Anita; Lucas, Trevor; Sioud, Mouldy; Aharinejad, Seyedhossein; Abraham, Dietmar. 2013. "Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts." Int. J. Mol. Sci. 14, no. 9: 17958-17971.