TY - JOUR
T1 - Adipose Stroma Accelerates the Invasion and Escape of Human Breast Cancer Cells from an Engineered Microtumor
AU - Dance, Yoseph W.
AU - Meshulam, Tova
AU - Seibel, Alex J.
AU - Obenreder, Mackenzie C.
AU - Layne, Matthew D.
AU - Nelson, Celeste M.
AU - Tien, Joe
N1 - Publisher Copyright:
© 2021, Biomedical Engineering Society.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - Fat
KW - Intravasation
KW - Lymphovascular invasion
KW - Microphysiological system
KW - Triple-negative breast cancer
KW - Tumor engineering
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U2 - 10.1007/s12195-021-00697-6
DO - 10.1007/s12195-021-00697-6
M3 - Article
C2 - 35096184
AN - SCOPUS:85113399404
SN - 1865-5025
VL - 15
SP - 15
EP - 29
JO - Cellular and Molecular Bioengineering
JF - Cellular and Molecular Bioengineering
IS - 1
ER -