Lactate-An Integrative Mirror of Cancer Metabolism.
Lactate-An Integrative Mirror of Cancer Metabolism.
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DOI：
10.1007/978-3-319-42118-6_2
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
S. Walenta;N. Voelxen;W. Mueller‐Klieser
中科院分区：
文献类型：
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作者：
S. Walenta;N. Voelxen;W. Mueller‐Klieser
诱导代谢生物发光成像（imBI）技术已被开发用于获得生物组织瞬时代谢状态的“快照”。使用速冻组织标本的冷冻切片，imBI将代谢物的高度特异性和敏感性原位检测与微观水平上的空间分辨率以及与组织组织学相关的代谢成像相结合。在这里，我们介绍了imBI在人类结直肠癌中的应用。将每个癌症的一次活检与2或3次活检的代谢信息进行比较，基于单次活检的高乳酸肿瘤与低乳酸肿瘤的分类反映了不同的糖酵解活性，在所有病例中，83%与多次活检的结果一致。我们进一步证明，肿瘤组织的代谢状态可以通过储存在液氮中至少保存10年以上，但不能通过储存在-80 °C。这意味着在− 180 ° C下可以长期保存代谢状态的组织库，这可能与癌症患者长期生存的研究有关。与其他肿瘤实体一样，组织乳酸盐浓度与结直肠癌的肿瘤发展和进展相关。首次诊断时，直肠正常组织和腺瘤的乳酸值较低，非转移性腺癌显著升高至中等水平，远处转移癌的乳酸值非常高。在相应条件下，组织葡萄糖浓度呈现相反的变化规律。单羧酸转运蛋白-4（MCT4）的表达水平与肿瘤乳酸浓度呈正相关，因此可能导致高乳酸肿瘤与高度恶性相关。
The technique of induced metabolic bioluminescence imaging (imBI) has been developed to obtain a “snapshot” of the momentary metabolic status of biological tissues. Using cryosections of snap-frozen tissue specimens, imBI combines highly specific and sensitive in situ detection of metabolites with a spatial resolution on a microscopic level and with metabolic imaging in relation to tissue histology. Here, we present the application of imBI in human colorectal cancer. Comparing the metabolic information of one biopsy with that of 2 or 3 biopsies per individual cancer, the classification into high versus low lactate tumors, reflecting different glycolytic activities, based on a single biopsy was in agreement with the result from multiple biopsies in 83 % of all cases. We further demonstrate that the metabolic status of tumor tissue can be preserved at least over 10 years by storage in liquid nitrogen, but not by storage at −80 °C. This means that tissue banking with long-term preservation of the metabolic status is possible at −180 °C, which may be relevant for studies on long-term survival of cancer patients. As with other tumor entities, tissue lactate concentration was shown to be correlated with tumor development and progression in colorectal cancer. At first-time diagnosis, lactate values were low in rectal normal tissue and adenomas, were significantly elevated to intermediate levels in non-metastatic adenocarcinomas, and were very high in carcinomas with distant metastasis. There was an inverse behavior of tissue glucose concentration under corresponding conditions. The expression level of monocarboxylate transporter-4 (MCT4) was positively correlated with the tumor lactate concentration and may thus contribute to high lactate tumors being associated with a high degree of malignancy.