The intermediary metabolism of the prostate: a key to understanding the pathogenesis and progression of prostate malignancy.
This review emphasizes the importance and role of altered intermediary metabolism of prostate cells in the pathogenesis of prostate adenocarcinoma (PCa) and the progression of malignancy. The focus of the presentation is a summary of the overwhelming evidence which implicates the metabolic transformation of citrate-producing sane cells to citrate-oxidizing malignant cells in the process of malignancy. The evidence now demonstrates that altered zinc accumulation is an important factor in this transformation. These metabolic relationships are uniquely different from the metabolic alterations associated with tumorigenesis of other mammalian cells. The metabolic transformation of zinc-accumulating citrate-producing normal prostate epithelial cells to citrate-oxidizing malignant cells has important implications on cellular bioenergetics, cell growth and apoptosis, lipogenesis, angiogenesis. Based on the metabolic considerations new concepts concerning the pathogenesis, diagnosis and treatment of prostate malignancy are presented. Unfortunately the metabolism of the prostate has been a seriously neglected and largely ignored area of prostate research. The importance of expanded research into the intermediary metabolism of normal and neoplastic prostate is essential to future significant advances in understanding and dealing with PCa.
Costello
L C
LC
Cellular and Molecular Biology Section, OCBS/Dental School, University of Maryland, Baltimore, MD, USA. lcc@dental.umaryland.edu
Franklin
R B
RB
D000818:Animals; D002471:Cell Transformation, Neoplastic; D019343:Citric Acid / Q000378:metabolism*; D002952:Citric Acid Cycle; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000628:therapy; D015032:Zinc / Q000378:metabolism*
D019343:Citric Acid; D005947:Glucose; D015032:Zinc