人肾细胞癌的代谢谱揭示了组织来源在营养利用率方面的优势。
Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability.
发表日期:2024 May 24
作者:
Keene L Abbott, Ahmed Ali, Bradley I Reinfeld, Amy Deik, Sonu Subudhi, Madelyn D Landis, Rachel A Hongo, Kirsten L Young, Tenzin Kunchok, Christopher S Nabel, Kayla D Crowder, Johnathan R Kent, Maria Lucia L Madariaga, Rakesh K Jain, Kathryn E Beckermann, Caroline A Lewis, Clary B Clish, Alexander Muir, W Kimryn Rathmell, Jeffrey Rathmell, Matthew G Vander Heiden
来源:
Food & Function
摘要:
肿瘤微环境是癌症进展和治疗效果的决定因素,其中营养物质的可用性发挥着重要作用。尽管已经确定特定营养素的局部丰度决定了肿瘤生长的代谢参数,但与正常组织和血液相比,指导肿瘤中营养素可用性的因素仍然知之甚少。为了确定肾细胞癌(RCC)中的这些因素,我们对肿瘤间质液(TIF)、邻近正常肾间质液(KIF)和从患者收集的血浆样本进行了定量代谢组学和综合脂质组学分析。 TIF 的营养成分与 KIF 非常相似,这表明与癌症存在无关的组织特异性因素对营养水平的影响比肿瘤驱动的变化更强。值得注意的是,在 RCC TIF 中发现了与 RCC 代谢已知特征一致的选择代谢变化,而 TIF 中的葡萄糖水平并未消耗到低于 KIF 中的水平。这些发现为肾细胞癌的组织营养动态提供了信息,强调了非癌症驱动的组织因子在塑造这些肿瘤的营养可用性方面的主导作用。© 2024,Abbott,Ali,Reinfeld 等。
The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it is established that the local abundance of specific nutrients defines the metabolic parameters for tumor growth, the factors guiding nutrient availability in tumor compared to normal tissue and blood remain poorly understood. To define these factors in renal cell carcinoma (RCC), we performed quantitative metabolomic and comprehensive lipidomic analyses of tumor interstitial fluid (TIF), adjacent normal kidney interstitial fluid (KIF), and plasma samples collected from patients. TIF nutrient composition closely resembles KIF, suggesting that tissue-specific factors unrelated to the presence of cancer exert a stronger influence on nutrient levels than tumor-driven alterations. Notably, select metabolite changes consistent with known features of RCC metabolism are found in RCC TIF, while glucose levels in TIF are not depleted to levels that are lower than those found in KIF. These findings inform tissue nutrient dynamics in RCC, highlighting a dominant role of non-cancer-driven tissue factors in shaping nutrient availability in these tumors.© 2024, Abbott, Ali, Reinfeld et al.