Cell proliferation, 2019-05, Vol.52 (3), p.e12600-n/a
2019
Details
- Autor(en) / Beteiligte
- Titel
- Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial‐mesenchymal transition in salivary adenoid cystic carcinoma
- Ist Teil von
- Cell proliferation, 2019-05, Vol.52 (3), p.e12600-n/a
- Ort / Verlag
- England: John Wiley & Sons, Inc
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- Wiley-Blackwell Full Collection
- Beschreibungen/Notizen
- Objectives To investigate the role of hypoxia in vasculogenic mimicry (VM) of salivary adenoid cystic carcinoma (SACC) and the underlying mechanism involved. Materials and methods Firstly, wound healing, transwell invasion, immunofluorescence and tube formation assays were performed to measure the effect of hypoxia on migration, invasion, EMT and VM of SACC cells, respectively. Then, immunofluorescence and RT‐PCR were used to detect the effect of hypoxia on VE‐cadherin and VEGFA expression. And pro‐vasculogenic mimicry effect of VEGFA was investigated by confocal laser scanning microscopy and Western blot. Moreover, the levels of E‐cadherin, N‐cadherin, Vimentin, CD44 and ALDH1 were determined by Western blot and immunofluorescence in SACC cells treated by exogenous VEGFA or bevacizumab. Finally, CD31/ PAS staining was performed to observe VM and immunohistochemistry was used to determine the levels of VEGFA and HIF‐1α in 95 SACC patients. The relationships between VM and clinicopathological variables, VEGFA or HIF‐1α level were analysed. Results Hypoxia promoted cell migration, invasion, EMT and VM formation, and enhanced VE‐cadherin and VEGFA expression in SACC cells. Further, exogenous VEGFA markedly increased the levels of N‐cadherin, Vimentin, CD44 and ALDH1, and inhibited the expression of E‐cadherin, while the VEGFA inhibitor reversed these changes. In addition, VM channels existed in 25 of 95 SACC samples, and there was a strong positive correlation between VM and clinic stage, distant metastases, VEGFA and HIF‐1α expression. Conclusions VEGFA played an important role in hypoxia‐induced VM through regulating EMT and stemness, which may eventually fuel the migration and invasion of SACC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-7722eISSN: 1365-2184DOI: 10.1111/cpr.12600Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6536414
- Format
- –
- Schlagworte
- Adenoid, Adult, Angiogenesis Inhibitors - pharmacology, Antigens, CD - genetics, Antigens, CD - metabolism, Bevacizumab, Bevacizumab - pharmacology, Cadherins - genetics, Cadherins - metabolism, Carcinoma, Adenoid Cystic - blood supply, Carcinoma, Adenoid Cystic - metabolism, Carcinoma, Adenoid Cystic - pathology, CD44 antigen, Cell adhesion & migration, Cell Line, Tumor, Cell migration, Cell Movement, Confocal microscopy, Epithelial-Mesenchymal Transition - genetics, Epithelial-Mesenchymal Transition - physiology, epithelial‐mesenchymal transition, Female, Gene Expression Regulation, Neoplastic, Growth factors, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit - metabolism, Immunofluorescence, Immunohistochemistry, Levels, Male, Mesenchyme, Metastases, Microscopy, Middle Aged, Mimicry, Monoclonal antibodies, Neoplasm Invasiveness, Neovascularization, Pathologic, Original, RNA, Messenger - genetics, RNA, Messenger - metabolism, salivary adenoid cystic carcinoma, Salivary Gland Neoplasms - blood supply, Salivary Gland Neoplasms - metabolism, Salivary Gland Neoplasms - pathology, Scanning microscopy, Tumor Hypoxia - physiology, Vascular endothelial growth factor, vascular endothelial growth factor A, Vascular Endothelial Growth Factor A - antagonists & inhibitors, Vascular Endothelial Growth Factor A - genetics, Vascular Endothelial Growth Factor A - metabolism, vasculogenic mimicry, Vimentin, Wound healing