Karen-Ng Lee Peng, James Emma Louise, Stephen Abish, Bennett Mark Henry, Mycielska Maria Elzbieta, Parkinson Eric Kenneth
Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AD, UK.
Oral Cancer Research & Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia.
Cancers (Basel). 2021 Aug 21;13(16):4212. doi: 10.3390/cancers13164212.
Premalignant oral lesions (PPOLs) which bypass senescence (IPPOL) have a much greater probability of progressing to malignancy, but pre-cancerous fields also contain mortal PPOL keratinocytes (MPPOL) that possess tumour-promoting properties. To identify metabolites that could potentially separate IPPOL, MPPOL and normal oral keratinocytes non-invasively in vivo, we conducted an unbiased screen of their conditioned medium. MPPOL keratinocytes showed elevated levels of branch-chain amino acid, lipid, prostaglandin, and glutathione metabolites, some of which could potentially be converted into volatile compounds by oral bacteria and detected in breath analysis. Extracellular metabolites were generally depleted in IPPOL, and only six were elevated, but some metabolites distinguishing IPPOL from MPPOL have been associated with progression to oral squamous cell carcinoma (OSCC) in vivo. One of the metabolites elevated in IPPOL relative to the other groups, citrate, was confirmed by targeted metabolomics and, interestingly, has been implicated in cancer growth and metastasis. Although our investigation is preliminary, some of the metabolites described here are detectable in the saliva of oral cancer patients, albeit at a more advanced stage, and could eventually help detect oral cancer development earlier.
绕过衰老的口腔癌前病变（IPPOL）发展为恶性肿瘤的可能性要大得多，但癌前区域也含有具有肿瘤促进特性的终末分化口腔癌前病变角质形成细胞（MPPOL）。为了确定能够在体内非侵入性地潜在区分IPPOL、MPPOL和正常口腔角质形成细胞的代谢物，我们对它们的条件培养基进行了无偏向筛选。MPPOL角质形成细胞的支链氨基酸、脂质、前列腺素和谷胱甘肽代谢物水平升高，其中一些可能被口腔细菌转化为挥发性化合物并在呼吸分析中检测到。IPPOL中的细胞外代谢物普遍减少，只有六种代谢物升高，但一些区分IPPOL和MPPOL的代谢物与体内进展为口腔鳞状细胞癌（OSCC）有关。通过靶向代谢组学证实，相对于其他组，IPPOL中升高的一种代谢物柠檬酸，有趣的是，它与癌症生长和转移有关。尽管我们的研究是初步的，但这里描述的一些代谢物在口腔癌患者的唾液中可以检测到，尽管处于更晚期阶段，最终可能有助于更早地检测口腔癌的发展。
