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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].”
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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].”
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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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