@article{90a12e2bdd07434c87cdb744fb9bbcd3,
title = "Adipose Stroma Accelerates the Invasion and Escape of Human Breast Cancer Cells from an Engineered Microtumor",
abstract = "Introduction: Approximately 20–25% of human breast tumors are found within an adipose, rather than fibrous, stroma. Adipose stroma is associated with an increased risk of lymph node metastasis, but the causal association between adipose stroma and metastatic progression in human breast cancer remains unclear. Methods: We used micropatterned type I collagen gels to engineer ~3-mm-long microscale human breast tumors within a stroma that contains adipocytes and adipose-derived stem cells (ASCs) (collectively, {"}adipose cells{"}). Invasion and escape of human breast cancer cells into an empty 120-μm-diameter lymphatic-like cavity was used to model interstitial invasion and vascular escape in the presence of adipose cell-derived factors for up to 16 days. Results: We found that adipose cells hasten invasion and escape by 1–2 days and 2–3 days, respectively. These effects were mediated by soluble factors secreted by the adipose cells, and these factors acted directly on tumor cells. Surprisingly, tumor invasion and escape were more strongly induced by ASCs than by adipocytes. Conclusions: This work reveals that both adipocytes and ASCs accelerate the interstitial invasion and escape of human breast cancer cells, and sheds light on the link between adipose stroma and lymphatic metastasis in human breast cancer.",
keywords = "Fat, Intravasation, Lymphovascular invasion, Microphysiological system, Triple-negative breast cancer, Tumor engineering",
author = "Dance, {Yoseph W.} and Tova Meshulam and Seibel, {Alex J.} and Obenreder, {Mackenzie C.} and Layne, {Matthew D.} and Nelson, {Celeste M.} and Joe Tien",
note = "Funding Information: We thank Stephen Farmer (Boston Nutrition Obesity Research Center; BNORC) for insightful discussions. This study was funded by award U01 CA214292 from the National Cancer Institute and by award P30 DK046200 from the National Institute of Diabetes and Digestive and Kidney Diseases. Y.W.D. was supported by a training grant from the National Institute of General Medical Sciences (award T32 GM008764) and by a fellowship from the CURE Diversity Research Supplements Program at the National Cancer Institute. Human ASCs were provided by the Adipocyte Core of BNORC. Yoseph W. Dance, Tova Meshulam, Alex J. Seibel, Mackenzie C. Obenreder, Matthew D. Layne, Celeste M. Nelson, and Joe Tien declare that they have no conflict of interest. No human or animal studies were carried out by the authors for this article. Funding Information: We thank Stephen Farmer (Boston Nutrition Obesity Research Center; BNORC) for insightful discussions. This study was funded by award U01 CA214292 from the National Cancer Institute and by award P30 DK046200 from the National Institute of Diabetes and Digestive and Kidney Diseases. Y.W.D. was supported by a training grant from the National Institute of General Medical Sciences (award T32 GM008764) and by a fellowship from the CURE Diversity Research Supplements Program at the National Cancer Institute. Human ASCs were provided by the Adipocyte Core of BNORC. Publisher Copyright: {\textcopyright} 2021, Biomedical Engineering Society.",
year = "2022",
month = feb,
doi = "10.1007/s12195-021-00697-6",
language = "English (US)",
volume = "15",
pages = "15--29",
journal = "Cellular and Molecular Bioengineering",
issn = "1865-5025",
publisher = "Springer New York",
number = "1",
}