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Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors
Open accessPublished version of a preprint
Abstract
Purpose: Adipose tissue contains a population of tumor-tropic mesenchymal progenitors, termed adipose stromal cells (ASC), which engraft in neighboring tumors to form supportive tumor stroma. We hypothesized that intra-abdominal visceral adipose tissue may contain a uniquely tumor-promoting population of ASC to account for the relationship between excess visceral adipose tissue and mortality of intra-abdominal cancers. Experimental Design: To investigate this, we isolated and characterized ASC from intra-abdominal omental adipose tissue (O-ASC) and characterized their effects on endometrial cancer progression as compared with subcutaneous adipose-derived mesenchymal stromal cells (SC-ASC), bone marrow–derived mesenchymal stromal cells (BM-MSC), and lung fibroblasts. To model chronic recruitment of ASC by tumors, cells were injected metronomically into mice bearing Hec1a xenografts. Results: O-ASC expressed cell surface markers characteristic of BM-MSC and differentiated into mesenchymal lineages. Coculture with O-ASC increased endometrial cancer cell proliferation in vitro. Tumor tropism of O-ASC and SC-ASC for human Hec1a endometrial tumor xenografts was comparable, but O-ASC more potently promoted tumor growth. Compared with tumors in SC-ASC–injected mice, tumors in O-ASC–injected mice contained higher numbers of large tortuous desmin-positive blood vessels, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. O-ASC exhibited enhanced motility as compared with SC-ASC in response to Hec1a-secreted factors. Conclusions: Visceral adipose tissue contains a population of multipotent MSCs that promote endometrial tumor growth more potently than MSCs from subcutaneous adipose tissue. We propose that O-ASCs recruited to tumors express specific factors that enhance tumor vascularization, promoting survival and proliferation of tumor cells. Clin Cancer Res; 18(3); 771–82. ©2011 AACR.
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“Both BM- and adipose-derived MSC display tumor tropism due to various tumor-released chemotactic factors including CCL25 [43], C-X-C motif chemokine-1 (CXCL1) [54], epidermal growth factor (EGF) [83, 84], hepatoma-derived growth factor (HDGF) [85], IL-8 [54], platelet-derived growth factor (PDGF) [84], stromal cell-derived factor-1 (SDF1, a.k.a. CXCL12) [86, 87], TGFβ [88], and VEGF [84].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [54]
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“Although all MSC populations share basic similarities immunophenotypically and functionally, differences can be demonstrated using high resolution techniques [52, 53] and are reflected in variability within their secretome [7, 54].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [54]
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“Subcutaneous adipose-derived MSC populations seem to secrete lower level of VEGF than BM-MSC [7, 54] or visceral ASC [54].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [54]
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Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development
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Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment
Onstad, M. A., Schmandt, R. E., & Lu, K. H. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.69.4638 · Cited by 667
Self-citationThe obese adipose tissue microenvironment in cancer development and progression
Quail, D. F., & Dannenberg, A. J. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0126-x · Cited by 542
Cancer as a Matter of Fat: The Crosstalk between Adipose Tissue and Tumors
Lengyel, E. R., Makowski, L., DiGiovanni, J., & Kolonin, M. G. (2018) · Trends in cancer · doi:10.1016/j.trecan.2018.03.004 · Cited by 436
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Metadata
- Authors
- Klopp, A. H., Zhang, Y., Solley, T., Amaya-Manzanares, F., Marini, F., Andreeff, M., Debeb, B., Woodward, W., Schmandt, R., Broaddus, R., Lu, K., & Kolonin, M. G.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Authors' Affiliations: Departments of 1Radiation Oncology, 2Leukemia, 3Gynecologic Oncology, and 4Pathology, The University of Texas MD Anderson Cancer Center; and 5The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas
- Corresponding author
- Kolonin, Mikhail G.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2012-01-31
- Volume
- 18
- Issue
- 3
- Pages
- 771-782
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC3481843
- OpenAlex
- W2126961122
- Cited by
- 178
- References
- 49
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 19 · 2022: 6 · 2021: 13 · 2020: 7 · 2019: 11 · 2018: 13 · 2017: 17 · 2016: 12 · 2015: 21 · 2014: 16 · 2013: 22 · 2012: 8
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (KG080782)
- National Cancer Institute (P50CA098258, P50CA140388, R01CA109451, RC1CA146381, P50CA083639, P30CA016672)
- National Institute of Neurological Disorders and Stroke (R01NS069964, R01NS06994)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- omental adipose tissue, adipose-derived stromal cells, endometrial cancer, tumor vascularization, tumor stroma, visceral adipose tissue, mesenchymal stem cells, tumor cell proliferation, tumor necrosis, cell motility, tumor microenvironment
- MeSH terms
- Adipose Tissue, Animals, Cell Differentiation, Female, Flow Cytometry, Humans, Neovascularization, Pathologic, Omentum, Transplantation, Heterologous, Endometrial Neoplasms, Stromal Cells, Subcutaneous Fat, Mice, Mesenchymal Stem Cells
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