Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability
Year: 2024
Type: preprint
Study design: Observational Study
Abstract: Summary 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.
Source: eLife
Authors: 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 C. Rathmell, Matthew G. Vander Heiden
Institutions: Broad Institute, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology, Vanderbilt University, Vanderbilt University Medical Center, Harvard University, Massachusetts General Hospital, Whitehead Institute for Biomedical Research, University of Chicago, University of Chicago Medical Center, University of Massachusetts Chan Medical School, Vanderbilt-Ingram Cancer Center, Amsterdam UMC Location Vrije Universiteit Amsterdam, Dana-Farber Cancer Institute
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Science Foundation, U.S. Department of Defense, Howard Hughes Medical Institute, American Association for Cancer Research, National Foundation for Cancer Research, Advanced Medical Research Foundation, National Institutes of Health, Ludwig Center for Molecular Oncology, National Cancer Institute, National Institute of General Medical Sciences
Awards: G1043181615, G13540369, G2046967885, G2143026252, G2347845466, Graduate Research Fellowship Program, Medical Scientist Training Program, G4201875207, Pre-Doctoral Training in Biological Sciences, Reengineering obesity-induced abnormal microenvironment to improve PDAC treatment, G9000118450, G9000148505, G9000196310, Improving treatment of HER2+ breast cancer brain metastasis by targeting lipid metabolism
OpenAlex ID: W4396544112