Mesenchymal-epithelial signalling in tumour microenvironment: role of high-mobility group Box 1
| Autor: | Elaine Hemers, Andrew Evans, Sikander Sharma |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Epithelium RAGE (receptor) Mesoderm Phosphatidylinositol 3-Kinases 0302 clinical medicine Invasion Cell Movement Tumor Microenvironment Medicine HMGB1 Protein Myofibroblasts HMGB1 biology Regular Article Recombinant Proteins Drug Combinations 030220 oncology & carcinogenesis Glucose deprivation Colonic Neoplasms Proteoglycans Collagen Mitogen-Activated Protein Kinases Myofibroblast Protein Binding Signal Transduction Stromal cell Histology MAP Kinase Signaling System Blotting Western chemical and pharmacologic phenomena Adenocarcinoma Pathology and Forensic Medicine RS 03 medical and health sciences QH301 Antigens Neoplasm Cell Line Tumor Humans PI3K/AKT/mTOR pathway Cell Proliferation Tumour microenvironment business.industry Mesenchymal stem cell Cell Biology Enzyme Activation Toll-Like Receptor 4 030104 developmental biology Glucose Culture Media Conditioned Cancer cell Immunology Cancer research biology.protein Laminin business |
| Zdroj: | Cell and Tissue Research |
| ISSN: | 1432-0878 |
| Popis: | Glucose deprivation, hypoxia and acidosis are characteristic features of the central core of most solid tumours. Myofibroblasts are stromal cells present in many such solid tumours, including those of the colon, and are known to be involved in all stages of tumour progression. HMGB1 is a nuclear protein with an important role in nucleosome stabilisation and gene transcription; it is also released from immune cells and is involved in the inflammatory process. We report that the microenvironmental condition of glucose deprivation is responsible for the active release of HMGB1 from various types of cancer cell lines (HT-29, MCF-7 and A549) under normoxic conditions. Recombinant HMGB1 (10 ng/ml) triggered proliferation in myofibroblast cells via activation of PI3K and MEK1/2. Conditioned medium collected from glucose-deprived HT-29 colon cancer cells stimulated the migration and invasion of colonic myofibroblasts, and these processes were significantly inhibited by immunoneutralising antibodies to HMGB1, RAGE and TLR4, together with specific inhibitors of PI3K and MEK1/2. Our data suggest that HMGB1 released from cancer cells under glucose deprivation is involved in stimulating colonic myofibroblast migration and invasion and that this occurs through the activation of RAGE and TLR4, resulting in the activation of the MAPK and PI3K signalling pathways. Thus, HMGB1 might be released by cancer cells in areas of low glucose in solid tumours with the resulting activation of myofibroblasts and is a potential therapeutic target to inhibit solid tumour growth. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|