Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion
| Autor: | Linhui Liang, Lei Liu, Hanwei Kong, Deshui Jia, Jinjun Li, Xianghuo He, Mingxia Yan, Xiaomin Wang, Ming Yao, Xiangfang Hao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Lung Neoplasms Blotting Western Fluorescent Antibody Technique Apoptosis Mice SCID Biology Adenocarcinoma lcsh:RC254-282 Metastasis Colony-Forming Units Assay Immunoenzyme Techniques Mice Cell Movement Mice Inbred NOD Genetics medicine Cell Adhesion Tumor Cells Cultured Animals Humans Epithelial–mesenchymal transition RNA Messenger Lung cancer Cell adhesion Cell Proliferation Wound Healing Cell growth Reverse Transcriptase Polymerase Chain Reaction Mesenchymal stem cell lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Fibronectins Fibronectin Disease Models Animal Phenotype Oncology biology.protein Stem cell Research Article |
| Zdroj: | BMC Cancer BMC Cancer, Vol 10, Iss 1, p 364 (2010) |
| ISSN: | 1471-2407 |
| Popis: | BackgroundThe formation of metastasis is the most common cause of death in patients with lung cancer. A major implement to understand the molecular mechanisms involved in lung cancer metastasis has been the lack of suitable models to address it. In this study, we aimed at establishing a highly metastatic model of human lung cancer and characterizing its metastatic properties and underlying mechanisms.MethodsThe human lung adeno-carcinoma SPC-A-1 cell line was used as parental cells for developing of highly metastatic cells byin vivoselection in NOD/SCID mice. After three rounds of selection, a new SPC-A-1sci cell line was established from pulmonary metastatic lesions. Subsequently, the metastatic properties of this cell line were analyzed, including optical imaging ofin vivometastasis, immunofluorescence and immunohistochemical analysis of several epithelial mesenchymal transition (EMT) makers and trans-well migration and invasion assays. Finally, the functional roles of fibronectin in the invasive and metastatic potentials of SPC-A-1sci cells were determined by shRNA analysis.ResultsA spontaneously pulmonary metastatic model of human lung adeno-carcinoma was established in NOD/SCID mice, from which a new lung cancer cell line, designated SPC-A-1sci, was isolated. Initially, the highly metastatic behavior of this cell line was validated by optical imaging in mice models. Further analyses showed that this cell line exhibit phenotypic and molecular alterations consistent with EMT. Compared with its parent cell line SPC-A-1, SPC-A-1sci was more aggressivein vitro, including increased potentials for cell spreading, migration and invasion. Importantly, fibronectin, a mesenchymal maker of EMT, was found to be highly expressed in SPC-A-1sci cells and down-regulation of it can decrease thein vitroandin vivometastatic abilities of this cell line.ConclusionsWe have successfully established a new human lung cancer cell line with highly metastatic potentials, which is subject to EMT and possibly mediated by increased fibronectin expression. This cell line and its reproducibles.c. mouse model can further be used to identify underlying mechanisms of lung cancer metastasis. |
| Databáze: | OpenAIRE |
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