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Hypothesis: Vitamin D restricts blood to prostate cancer cells – June 2013

Role of androgen and vitamin D receptors in endothelial cells from benign and malignant human prostate

AJP - Endo June 1, 2013 vol. 304 no. 11 E1131-E1139
Alejandro S. Godoy 1,3,4,*,
Ivy Chung 6,7,*,
Viviana P. Montecinos 2,3,
Ralph Buttyan 8,
Candace S. Johnson 5, and
Gary J. Smith 4
1Department of Physiology,
2Department of Hematology Oncology, and
3Center for Translational Research in Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile;
4Department of Urology and
5Department of Pharmacology, Roswell Park Cancer Institute, Buffalo, New York;
6Department of Pharmacology, Faculty of Medicine, and
7University of Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia; and
8Vancouver Prostate Centre, Vancouver, British Columbia, Canada
Address for reprint requests and other correspondence: A. S. Godoy, Dept. of Physiology, Pontificia Universidad Católica de Chile, Alameda 340, Santiago de Chile (e-mail: agodoy at bio.puc.cl).

Forty years ago, Judah Folkman (Folkman. N Engl J Med 285: 1182–1186, 1971) proposed that tumor growth might be controlled by limiting formation of new blood vessels (angiogenesis) needed to supply a growing tumor with oxygen and nutrients. To this end, numerous “antiangiogenic” agents have been developed and tested for therapeutic efficacy in cancer patients, including prostate cancer (CaP) patients, with limited success. Despite the lack of clinical efficacy of lead anti-angiogenic therapeutics in CaP patients, recent published evidence continues to support the idea that prostate tumor vasculature provides a reasonable target for development of new therapeutics. Particularly relevant to antiangiogenic therapies targeted to the prostate is the observation that specific hormones can affect the survival and vascular function of prostate endothelial cells within normal and malignant prostate tissues.

Here, we review the evidence demonstrating that both androgen(s) and vitamin D significantly impact the growth and survival of endothelial cells residing within prostate cancer and that systemic changes in circulating androgen or vitamin D drastically affect blood flow and vascularity of prostate tissue. Furthermore, recent evidence will be discussed about the expression of the receptors for both androgen and vitamin D in prostate endothelial cells that argues for direct effects of these hormone-activated receptors on the biology of endothelial cells.

Based on this literature, we propose that prostate tumor vasculature represents an unexplored target for modulation of tumor growth. A better understanding of androgen and vitamin D effects on prostate endothelial cells will support development of more effective angiogenesis-targeting therapeutics for CaP patients.

See also VitaminDWiki

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