Citrate alterations in primary and metastatic human prostatic adenocarcinomas:1H magnetic resonance spectroscopy and biochemical study

摘要

AbstractThe objectives of this study were to quantitatively verify the low levels of citrate previously observed in primary human prostatic adenocarcinomas and to determine whether citrate was further reduced in metastatic prostatic cancer. This was accomplished by comparison of citrate concentrations of DU 145 xenografts (a poorly differentiated human prostatic adenocarcinoma cell line grown in nude mice) with concentrations in primary human adenocarcinomas. Followingin vivo1H NMR studies of DU 145 xenografts, citrate concentrations of DU 145 xenografts and surgically removed primary prostatic adenocarcinoma tissue were determined by quantitative high resolution1H NMR and enzymatic assay. The most significant findings of this study were that citrate concentrations in primary human adenocarcinomas (3.74 ± 0.19 μmolJg wet weight) were significantly lower than those observed for normal and benign hyperplastic (BPH) prostatic tissues. Furthermore there was a further ten‐fold reduction of citrate associated with DU 145 xenografts (0.31 ± 0.028 μmoleJg wet weight) compared with primary prostatic cancer. DU 145 xenografts also exhibited higher levels of uridine diphosphosugars and choline containing metabolites relative to primary prostatic adenocarcinomas. These findings support the hypothesis that citrate is low in primary prostatic cancer and further reduced in metastatic di