title: Interactions among Lung Cancer Cells, Fibroblasts, and Macrophages in 3D Co-Cultures and the Impact on MMP-1 and VEGF Expression.
abstract: In vitro cell-based models of lung cancer are frequently employed to study invasion and the mechanisms behind metastasis. However, these models often study only one cell type with two-dimensional (2D) monolayer cell cultures, which do not accurately reflect the complexity of inflammation in vivo. Here, a three-dimensional (3D) cell co-culture collagen gel model was employed, containing human lung adenocarcinoma cells (HCC), human lung fibroblast cells (MRC-5), and macrophages. Cell culture media and cell images were collected, and matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor (VEGF) production was monitored under different cell culture conditions. We found that simulating hypoxia and/or serum starvation conditions induced elevated secretion of VEGF in the 3D co-culture model in vitro, but not MMP-1; the morphology of HCC in the 2D versus the 3D co-culture system was extremely different. MMP-1 and VEGF were secreted at higher levels in mixed cell groups rather than mono-culture groups. Therefore, incorporating lung cancer cells, fibroblasts, and macrophages may better reflect physiological metastasis mechanisms compared to mono-culture systems. Tumour stromal cells, macrophages, and fibroblast cells may promote invasion and metastasis, which also provides a new direction for the design of therapies targeted at destroying the stroma of tumor tissues.
authors.affiliation: Division of Respiratory Medicine and Thoracic Oncology, Medizinische Klinik V, Ludwig-Maximilians University (LMU), Thoracic Oncology Centre Munich, Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research (DZL), Munich, Bavaria, Germany.|Department of medical oncology, First people's hospital of Lianyungang city, Lianyungang, Jiangsu, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Liu
authors.affiliation: Division of Respiratory Medicine and Thoracic Oncology, Medizinische Klinik V, Ludwig-Maximilians University (LMU), Thoracic Oncology Centre Munich, Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research (DZL), Munich, Bavaria, Germany.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Kiefl
authors.affiliation: Division of Hematooncology, Medizinische Klinik-Innenstadt, Ludwig-Maximilians University (LMU), Munich, Bavaria, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Roskopf
authors.affiliation: Division of Respiratory Medicine and Thoracic Oncology, Medizinische Klinik V, Ludwig-Maximilians University (LMU), Thoracic Oncology Centre Munich, Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research (DZL), Munich, Bavaria, Germany.
authors.forename: Fei
authors.initials: F
authors.lastname: Tian
authors.affiliation: Division of Respiratory Medicine and Thoracic Oncology, Medizinische Klinik V, Ludwig-Maximilians University (LMU), Thoracic Oncology Centre Munich, Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research (DZL), Munich, Bavaria, Germany.
authors.forename: Rudolf M
authors.initials: RM
authors.lastname: Huber
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D002450:Cell Communication; D045744:Cell Line, Tumor; D018920:Coculture Techniques / Q000379:methods*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D020781:Matrix Metalloproteinase 1