Introduction

Interstitial hypertension, a rise in interstitial fluid pressure, is a common feature of many solid tumors as they progress to an invasive state. It is currently unclear whether this elevated pressure alters the probability that tumor cells eventually escape into a neighboring blood or lymphatic vessel.

Methods

In this study, we analyze the escape of MDA-MB-231 human breast tumor cells from a ~3-mm-long preformed aggregate into a 120-μm-diameter empty cavity in a micromolded type I collagen gel. The “micro-tumors” were located within ~300 μm of one or two cavities. Pressures of ~0.65 cm H₂O were applied only to the tumor (“interstitial hypertension”) or to its adjacent cavity.

Results

This work shows that interstitial hypertension suppresses escape into the adjacent cavity, but not because tumor cells respond directly to the pressure profile. Instead, hypertension alters the chemical microenvironment at the tumor margin to one that hampers escape. Administration of tumor interstitial fluid phenocopies the effects of hypertension.

Conclusions

This work uncovers a link between tumor pressure, interstitial flow, and tumor cell escape in MDA-MB-231 cells, and suggests that interstitial hypertension serves to hinder further progression to metastatic escape.

中文翻译：

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间质性高血压通过间质液对流抑制人类乳腺肿瘤细胞的逃逸

介绍

间质性高血压是间质液压力的升高，是许多实体瘤发展为侵袭性状态时的共同特征。目前尚不清楚这种升高的压力是否会改变肿瘤细胞最终逃逸到邻近血液或淋巴管中的可能性。

方法

在这项研究中，我们分析了 MDA-MB-231 人乳腺肿瘤细胞从约 3 毫米长的预成型聚集体中逃逸到微成型 I 型胶原凝胶中直径为 120微米的空腔中。“微型肿瘤”位于一个或两个空腔的约 300微米范围内。约0.65 cm H ₂ O 的压力仅应用于肿瘤（“间质性高血压”）或其邻近腔。

结果

这项工作表明，间质性高血压抑制逃逸到相邻腔，但不是因为肿瘤细胞直接对压力分布作出反应。相反，高血压将肿瘤边缘的化学微环境改变为一种阻碍逃逸的微环境。肿瘤间质液的给药表现出高血压的影响。

结论

这项工作揭示了 MDA-MB-231 细胞中肿瘤压力、间质流动和肿瘤细胞逃逸之间的联系，并表明间质性高血压有助于阻碍进一步进展为转移性逃逸。