Research Papers:

Cancer-associated fibroblasts promote non-small cell lung cancer cell invasion by upregulation of glucose-regulated protein 78 (GRP78) expression in an integrated bionic microfluidic device

Ting Yu _, Zhe Guo, Hui Fan, Jing Song, Yuanbin Liu, Zhancheng Gao and Qi Wang

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Oncotarget. 2016; 7:25593-25603. https://doi.org/10.18632/oncotarget.8232

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Ting Yu1,*, Zhe Guo1,*, Hui Fan2,*, Jing Song1, Yuanbin Liu1,3, Zhancheng Gao4, Qi Wang1

1Department of Respiratory Medicine, The Second Hospital, Dalian Medical University, Dalian, China

2Department of Oncology, The Second Hospital, Dalian Medical University, Dalian, China

3Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, China

4Department of Respiratory & Critical Care Medicine, the People’s Hospital of Peking University, Beijing, China

*These authors have contributed equally to this work

Correspondence to:

Qi Wang, e-mail: [email protected]

Zhancheng Gao, e-mail: [email protected]

Keywords: cancer-associated fibroblasts, lung cancer, invasion, GRP78, microfluidic chip

Received: January 09, 2016    Accepted: March 04, 2016    Published: March 21, 2016


The tumor microenvironment is comprised of cancer cells and various stromal cells and their respective cellular components. Cancer-associated fibroblasts (CAFs), a major part of the stromal cells, are a key determinant in tumor progression, while glucose-regulated protein (GRP)78 is overexpressed in many human cancers and is involved in tumor invasion and metastasis. This study developed a microfluidic-based three dimension (3D) co-culture device to mimic an in vitro tumor microenvironment in order to investigate tumor cell invasion in real-time. This bionic chip provided significant information regarding the role of GRP78, which may be stimulated by CAFs, to promote non-small cell lung cancer cell invasion in vitro. The data showed that CAF induced migration of NSCLC A549 and SPCA-1 cells in this three-dimensional invasion microdevice, which is confirmed by using the traditional Transwell system. Furthermore, CAF induced GRP78 expression in A549 and SPCA-1 cells to facilitate NSCLC cell migration and invasion, whereas knockdown of GRP78 expression blocked A549 and SPCA-1 cell migration and invasion capacity. In conclusion, these data indicated that CAFs might promote NSCLC cell invasion by up-regulation of GRP78 expression and this bionic chip microdevice is a robust platform to assess the interaction of cancer and stromal cells in tumor environment study.

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