title: 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.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, The Second Hospital, Dalian Medical University, Dalian, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Respiratory Medicine, The Second Hospital, Dalian Medical University, Dalian, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Oncology, The Second Hospital, Dalian Medical University, Dalian, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Respiratory Medicine, The Second Hospital, Dalian Medical University, Dalian, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Respiratory Medicine, The Second Hospital, Dalian Medical University, Dalian, China.|Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yuanbin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Respiratory & Critical Care Medicine, The People's Hospital of Peking University, Beijing, China.
authors.forename: Zhancheng
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Respiratory Medicine, The Second Hospital, Dalian Medical University, Dalian, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018920:Coculture Techniques; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D009361:Neoplasm Invasiveness / Q000473:pathology; D059016:Tumor Microenvironment; D015854:Up-Regulation
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins
keywords: GRP78; cancer-associated fibroblasts; invasion; lung cancer; microfluidic chip