Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth
Open accessAbstract
Intra-abdominal tumors, such as ovarian cancer, have a clear predilection for metastasis to the omentum, an organ primarily composed of adipocytes. Currently, it is unclear why tumor cells preferentially home to and proliferate in the omentum, yet omental metastases typically represent the largest tumor in the abdominal cavities of women with ovarian cancer. We show here that primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells, and that adipokines including interleukin-8 (IL-8) mediate these activities. Adipocyte-ovarian cancer cell coculture led to the direct transfer of lipids from adipocytes to ovarian cancer cells and promoted in vitro and in vivo tumor growth. Furthermore, coculture induced lipolysis in adipocytes and β-oxidation in cancer cells, suggesting adipocytes act as an energy source for the cancer cells. A protein array identified upregulation of fatty acid-binding protein 4 (FABP4, also known as aP2) in omental metastases as compared to primary ovarian tumors, and FABP4 expression was detected in ovarian cancer cells at the adipocyte-tumor cell interface. FABP4 deficiency substantially impaired metastatic tumor growth in mice, indicating that FABP4 has a key role in ovarian cancer metastasis. These data indicate adipocytes provide fatty acids for rapid tumor growth, identifying lipid metabolism and transport as new targets for the treatment of cancers where adipocytes are a major component of the microenvironment.
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Adipocytes constitute a significant stromal component in the tumor microenvironment of several malignancies, including breast, ovarian, and colorectal cancers.
“Adipocytes constitute a significant stromal component in the TME of several malignancies, including breast, ovarian, and colorectal cancers [57,58].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [57]
The supplied passages describe adipocytes in the ovarian cancer metastatic microenvironment and identify breast tissue as an adipocyte-rich environment. They also report coculturing colon cancer cells with adipocytes, but do not establish that adipocytes are a significant stromal component of colorectal tumors. The claim extends beyond what this paper shows for colorectal cancer. (LLM, conf=0.85)
Experimental — accuracy not yet measuredUpregulation of FABP4 on metastatic ovarian cancer cells allows acquisition of fatty acids from omental adipocytes.
“upregulation of a long chain fatty acid-binding protein FABP4 on the surface of metastatic ovarian cancer cells allows them to acquire fatty acids directly from the adipocytes of the omental fat”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Nieman et al., 2011
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- Authors
- Nieman, K. M., Kenny, H. A., Penicka, C. V., Ladanyi, A., Buell-Gutbrod, R., Zillhardt, M. R., Romero, I. L., Carey, M. S., Mills, G. B., Hotamisligil, G. S., Yamada, S. D., Peter, M. E., Gwin, K., & Lengyel, E.
- Affiliations
- University of Chicago (US)
- The University of Texas MD Anderson Cancer Center (US)
- Northwestern University (US)
- Corresponding author
- Lengyel, Ernst
- ORCID
- Venue
- Nature Medicine
- Published
- 2011-10-30
- Volume
- 17
- Issue
- 11
- Pages
- 1498-1503
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4157349
- OpenAlex
- W2041237929
- Cited by
- 2,279
- References
- 37
- Citations by year
- 2026: 132 · 2025: 152 · 2024: 195 · 2023: 194 · 2022: 224 · 2021: 224 · 2020: 225 · 2019: 180 · 2018: 166 · 2017: 147 · 2016: 128 · 2015: 91 · 2014: 91 · 2013: 76 · 2012: 48
- FWCI
- 23.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (4r01ca111882-10)
- National Cancer Institute (R01-CA111882, P50CA098258, R01CA169604, L30 CA153336, K99CA134750, U01CA151461, T32 CA959421, T32CA009594, P30CA016672)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064360)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD000849)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- ovarian cancer, omental metastasis, adipocytes, tumor microenvironment, adipokines, interleukin-8, FABP4, lipid transfer, tumor cell migration and invasion, lipolysis, fatty acid beta-oxidation, tumor growth, peritoneal fat
- MeSH terms
- Animals, Female, Humans, Mice, Nude, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Transplantation, Omentum, Ovarian Neoplasms, Peritoneal Neoplasms, Tumor Cells, Cultured, Adipocytes, Coculture Techniques, Lipid Metabolism, Fatty Acid-Binding Proteins, Mice
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