alphaB-crystallin stimulates VEGF secretion and tumor cell migration and correlates with enhanced distant metastasis in head and neck squamous cell carcinoma
SourceBMC Cancer, 13, (2013), article 128
Article / Letter to editor
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Paediatrics - OUD tm 2017
Laboratory of Genetic, Endocrine and Metabolic Diseases
Radboud Institute for Molecular Life Sciences
Nijmegen Centre for Molecular Life Sciences
SubjectBio-Molecular Chemistry; IGMD 6: Hormonal regulation ONCOL 5: Aetiology, screening and detection; ONCOL 3: Translational research
BACKGROUND: alphaB-crystallin is able to modulate vascular endothelial growth factor (VEGF) secretion. In many solid tumors VEGF is associated with angiogenesis, metastasis formation and poor prognosis. We set out to assess whether alphaB-crystallin expression is correlated with worse prognosis and whether this is related to VEGF secretion and cell motility in head and neck squamous cell carcinoma (HNSCC). METHODS: alphaB-crystallin expression was determined immunohistochemically in tumor biopsies of 38 HNSCC patients. Locoregional control (LRC) and metastasis-free survival (MFS) of the patients were analyzed in relation to alphaB-crystallin expression. Additionally, the effects of alphaB-crystallin knockdown on VEGF secretion and cell motility were studied in vitro. RESULTS: Patients with higher staining fractions of alphaB-crystallin exhibited a significantly shorter MFS (Log-Rank test, p < 0.005). Under normoxic conditions alphaB-crystallin knockdown with two different siRNAs in a HNSCC cell line reduced VEGF secretion 1.9-fold and 2.1-fold, respectively. Under hypoxic conditions, a similar reduction of VEGF secretion was observed, 1.9-fold and 2.2-fold, respectively. The effect on cell motility was assessed by a gap closure assay, which showed that alphaB-crystallin knockdown decreased the rate by which HNSCC cells were able to close a gap by 1.5- to 2.0-fold. CONCLUSIONS: Our data suggest that alphaB-crystallin expression is associated with distant metastases formation in HNSCC patients. This association might relate to the chaperone function of alphaB-crystallin in mediating folding and secretion of VEGF and stimulating cell migration.
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