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

被引：8

作者：

An, Fan ^{[1
]}

Hou, Zhijie ^{[1
,8
]}

Wang, Xiaochao ^{[1
]}

Wang, Zhongmin ^{[7
]}

Jing, Chenying ^{[1
]}

Sui, Ran ^{[1
]}

Wu, Yameng ^{[1
]}

Ma, Yunfeng ^{[1
]}

Chang, Cheng ^{[1
]}

Liu, Shuai ^{[1
]}

Li, Manman ^{[1
]}

Sun, Lijie ^{[3
]}

Gao, Ziqi ^{[1
]}

Zhang, Wenjuan ^{[1
]}

Lang, Zhenghui ^{[1
]}

Zhao, Jiaqi ^{[1
]}

Qu, Yueyang ^{[4
]}

Xu, Lingzhi ^{[3
]}

Luo, Yong ^{[5
,6
]}

Yan, Jinsong ^{[8
]}

Wang, Yuesheng ^{[1
]}

Xu, Jie ^{[1
,9
]}

Liu, Quentin ^{[1
,2
,9
]}

机构：

[1] Dalian Med Univ, Inst Canc Stem Cell, Dalian 116044, Liaoning, Peoples R China

[2] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China

[3] Dalian Med Univ, Dept Oncol, Hosp 2, Dalian 116023, Liaoning, Peoples R China

[4] Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China

[5] Dalian Univ Technol, Dept Chem Engn, State Key Lab Fine Chem, Dalian 116024, Peoples R China

[6] Dalian Univ Technol, Sch Pharmaceut Sci & Technol, Dalian 116024, Peoples R China

[7] Dalian Municipal Women & Childrens Med Ctr, 1 Planning Rd, Dalian 116037, Liaoning, Peoples R China

[8] Dalian Med Univ, Diamond Bay Inst Hematol, Liaoning Med Ctr Hematopoiet Stem Cell Transplanta, Dept Hematol,Dalian Key Lab Hematol,, Dalian 116027, Liaoning, Peoples R China

[9] Dalian Med Univ, Inst Canc Stem Cell, 9 Western Sect,Lvshun South St, Dalian 116044, Liaoning, Peoples R China

来源：

BIOMATERIALS | 2022年 / 290卷

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

MSCs; Microfluidic device; Migration; H19; Hypoxia; Aspirin; BREAST-CANCER; STROMAL CELLS; METASTASIS; ASPIRIN;

D O I：

10.1016/j.biomaterials.2022.121848

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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.

引用

页数：11

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