Metabolic reprogramming and validation of hyperpolarized 13C lactate as a prostate cancer biomarker using a human prostate tissue slice culture bioreactor.
Metabolic reprogramming and validation of hyperpolarized 13C lactate as a prostate cancer biomarker using a human prostate tissue slice culture bioreactor.
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DOI：
10.1002/pros.22665
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发表时间：
2013-08
期刊：
影响因子：
2.8
通讯作者：
Kurhanewicz, John
中科院分区：
文献类型：
--
作者：
Keshari, Kayvan R.;Sriram, Renuka;Van Criekinge, Mark;Wilson, David M.;Wang, Zhen J.;Vigneron, Daniel B.;Peehl, Donna M.;Kurhanewicz, John
前列腺癌的治疗一直受到缺乏临床相关疾病模型和跟踪肿瘤进展的代谢标志物的阻碍。超极化（HP）~（13）C磁共振波谱已成为一种新技术，以研究前列腺癌的代谢变化。在这项研究中，我们研究了葡萄糖重编程使用HP 13 C丙酮酸MR在患者来源的前列腺组织切片培养（TSC）模型。评估新鲜切除的人前列腺TSCs中的稳态代谢物浓度，并与速冻活检样品中的稳态代谢物浓度进行比较。然后将TSCs应用于灌注细胞（生物反应器）平台，并分别通过31 P和HP 13 C MR研究TSCs的生物能量学和动态丙酮酸通量。前列腺TSC表现出稳态糖酵解和磷脂代谢，以及概括体内前列腺癌特征的生物能量学。与良性前列腺TSC相比，注射HP 13 C丙酮酸盐后的13 C光谱显示恶性肿瘤中丙酮酸盐至乳酸盐的通量显著增加。恶性前列腺TSC中的这种增加的通量与单羧酸转运体（MCT）的表达增加和乳酸脱氢酶（LDH）的活性增加两者相关。我们提供了HP 13 C乳酸盐作为活体人体组织中前列腺癌生物标志物的第一个机制证据，这对于体内研究的解释至关重要。更广泛地说，临床相关的代谢模型系统与HP MR相结合可以促进前列腺癌存在、侵袭性和治疗反应的临床可转化生物标志物的鉴定。
The treatment of prostate cancer has been impeded by the lack of both clinically relevant disease models and metabolic markers that track tumor progression. Hyperpolarized (HP) 13C MR spectroscopy has emerged as a new technology to investigate the metabolic shifts in prostate cancer. In this study, we investigate the glucose reprogramming using HP 13C pyruvate MR in a patient-derived prostate tissue slice culture (TSC) model. The steady-state metabolite concentrations in freshly excised human prostate TSCs were assessed and compared to those from snap-frozen biopsy samples. The TSCs were then applied to a perfused cell (bioreactor) platform, and the bioenergetics and the dynamic pyruvate flux of the TSCs were investigated by 31P and HP 13C MR, respectively. The prostate TSCs demonstrated steady-state glycolytic and phospholipid metabolism, and bioenergetics that recapitulate features of prostate cancer in vivo. 13C spectra following injection of HP 13C pyruvate showed significantly increased pyruvate to lactate flux in malignant as compared to the benign prostate TSCs. This increased flux in the malignant prostate TSCs correlated with both increased expression of monocarboxylate transporters (MCT) and activity of lactate dehydrogenase (LDH). We provide the first mechanistic evidence for HP 13C lactate as a prostate cancer biomarker in living human tissues, critical for the interpretation of in vivo studies. More broadly, the clinically relevant metabolic model system in combination with HP MR can facilitate the identification of clinically translatable biomarkers of prostate cancer presence, aggressiveness, and treatment response.
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影响因子：
3.6
作者：
Blauer, M.;Tammela, T. L.;Ylikomi, T.
通讯作者：
Ylikomi, T.
影响因子：
3.3
作者：
Keshari, Kayvan R.;Kurhanewicz, John;Jeffries, Rex E.;Wilson, David M.;Dewar, Brian J.;Van Criekinge, Mark;Zierhut, Matthew;Vigneron, Daniel B.;Macdonald, Jeffrey M.
通讯作者：
Macdonald, Jeffrey M.
DOI：
10.1073/pnas.0609299104
发表时间：
2007-04-24
影响因子：
11.1
作者：
Hallstrom, Taija M. Kiviharju-af;Jaamaa, Sari;Laiho, Marikki
通讯作者：
Laiho, Marikki
影响因子：
6.6
作者：
Han, M;Partin, AW;Walsh, PC
通讯作者：
Walsh, PC
影响因子：
4.1
作者：
Dimmer, KS;Friedrich, B;Bröer, S
通讯作者：
Bröer, S