Biological Sciences Division
Published May 24, 2024 | Version v1
Journal article Open

Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability

Creators

  • 1. Massachusetts Institute of Technology
  • 2. Vanderbilt University
  • 3. Broad Institute
  • 4. Harvard University
  • 5. Whitehead Institute for Biomedical Research
  • 6. University of Chicago

Description

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.

Data availability

All data generated or analyzed during the student are included with the manuscript and supporting files.

The following previously published data sets were used:

Wishart DS Guo A Oler E Wang F Anjum A Peters H Dizon R Sayeeda Z Tian S Lee BL Berjanskii M Mah R Yamamoto M Jovel J Torres-Calzada C Hiebert-Giesbrecht M Lui VW Varshavi D Varshavi D Allen D Arndt D Khetarpal N Sivakumaran A Harford K Sanford S Yee K Cao X Budinski Z Liigand J Zhang L Zheng J Mandal R Karu N Dambrova M Schiöth HB Greiner R Gautam V (2022) HMDB5.0 ID HMDB 5.0. HMDB 5.0: the Human Metabolome Database for 2022. http://www.hmdb.ca/

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Additional details

Identifiers

DOI
10.7554/eLife.95652.3
Other
oai:uchicago.tind.io:12443

Funding

National Science Foundation
DGE-1122374
National Cancer Institute
F31CA271787
National Institutes of Health
T32GM007287
Howard Hughes Medical Institute
Medical Research Fellowship
National Cancer Institute
F30CA247202
National Institutes of Health
T32GM007347
American Association for Cancer Research
National Institutes of Health
U01-CA224348
National Institutes of Health
R01-CA259253
National Institutes of Health
R01-CA208205
National Institutes of Health
R01-NS118929
National Institutes of Health
U01CA261842
Harvard University
Nile Albright Research Foundation
National Foundation for Cancer Research
Jane's Trust Foundation
Department of Defense
Education Activity
National Cancer Institute
R01CA217987
Massachusetts Institute of Technology
National Cancer Institute
R35CA242379
National Cancer Institute
P30CA1405141

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Ben May Department for Cancer Research, Surgery