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.

中文翻译：

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脂肪基质加速人类乳腺癌细胞从工程微肿瘤中的侵袭和逃逸

介绍

大约 20-25% 的人类乳腺肿瘤存在于脂肪而不是纤维基质中。脂肪基质与淋巴结转移风险增加有关，但脂肪基质与人类乳腺癌转移进展之间的因果关系仍不清楚。

方法

我们使用微图案 I 型胶原凝胶在含有脂肪细胞和脂肪干细胞 (ASC)（统称为“脂肪细胞”）的基质内设计了约 3 毫米长的微型人类乳腺肿瘤。人类乳腺癌细胞侵入和逃逸到直径为 120 微米的空淋巴样腔中，用于模拟在脂肪细胞衍生因子存在下长达 16 天的间质侵入和血管逃逸。

结果

我们发现脂肪细胞分别在 1-2 天和 2-3 天加速入侵和逃逸。这些作用是由脂肪细胞分泌的可溶性因子介导的，这些因子直接作用于肿瘤细胞。令人惊讶的是，ASCs 比脂肪细胞更强烈地诱导肿瘤侵袭和逃逸。

结论

这项工作揭示了脂肪细胞和 ASCs 都加速了人乳腺癌细胞的间质侵袭和逃逸，并阐明了脂肪基质与人乳腺癌淋巴转移之间的联系。