4.8 Article

A microfluidic demonstration of ?cluster-sprout-infiltrating? mode for hypoxic mesenchymal stem cell guided cancer cell migration

期刊

BIOMATERIALS
卷 290, 期 -, 页码 -

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121848

关键词

MSCs; Microfluidic device; Migration; H19; Hypoxia; Aspirin

资金

  1. National Key R&D Program of China [2019YFA0110300]
  2. Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China [IRT_17R15]
  3. Innovative Research Team in University of Liaoning [LT2017001]
  4. Science and Technology Innovation Foundation of Dalian [2020JJ25CY008]
  5. International Scientific and Technological Cooperation of Dalian [2015F11GH095]
  6. National Natural Science Foundation of China [81820108024, 81630005, 81972786, 81502579, 81703091]
  7. Shenzhen Bay Laboratory Research Funds [SZBL2021080601001]

向作者/读者索取更多资源

Mesenchymal stem cells (MSCs) play a critical role in promoting tumor metastasis, particularly in breast cancer. Through the use of a microfluidic-based 3D co-culture device, it was observed that MSCs guide cancer cell migration and accelerate invasion in a hypoxic microenvironment. The upregulation of H19 under hypoxic conditions was found to be important in MSCs-mediated cancer cell invasion. Aspirin was shown to suppress H19 expression and inhibit MSCs infiltration, leading to reduced breast cancer cell invasion.
Mesenchymal stem cells (MSCs) play a critical role in tumor metastasis. However, the dynamic process of MSCsmediated cancer cell invasion remains inconclusive. In breast cancer mouse models, we observed that MSCs promoted lung metastasis. We constructed a microfluidic-based 3D co-culture device to monitor MSCs-mediated cancer cell invasion in a nutrient-deficient hypoxic microenvironment. On biomimetic microfluidic devices, MSCs guided cancer cell migration in a cluster-sprout-infiltrating mode. Importantly, hypoxic conditions significantly promoted MSCs migration at the infiltration stage, leading to accelerated breast cancer cell invasion. Moreover, hypoxia related LncRNA analysis showed that H19 was dramatically upregulated in response to hypoxic conditions. Conversely, H19 depletion impaired MSCs-directed breast cancer cell invasion. Mechanistically, H19 functions as a competitive endogenous RNA (ceRNA) which sequesters miRNA let-7 to release its target matrix metalloproteinase-1 (MMP1). Intriguingly, aspirin dramatically suppressed H19 and MMP1 expression and blocked MSCs infiltration under hypoxic conditions, resulting in alleviated breast cancer cell invasion. These findings point to the metastatic promoting role of MSCs in tumor stroma and suggest that MSCs might be a therapeutic target for metastatic breast cancer.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据