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Open Access Research article

αB-crystallin stimulates VEGF secretion and tumor cell migration and correlates with enhanced distant metastasis in head and neck squamous cell carcinoma

Chantal van de Schootbrugge1, Johan Bussink2, Paul N Span2, Fred CGJ Sweep3, Reidar Grénman4, Hanneke Stegeman2, Ger JM Pruijn1, Johannes HAM Kaanders2 and Wilbert C Boelens15*

Author Affiliations

1 Department of Biomolecular Chemistry, Institute for Molecules and Materials and Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands

2 Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, 6500 HB, The Netherlands

3 Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, 6500 HB, The Netherlands

4 Department of Otorhinolaryngology–Head and Neck Surgery, Turku University Hospital, PO Box 52, Turku, FI-20521, Finland

5 Biomolecular Chemistry 271, NCMLS, Radboud University Nijmegen, PO Box 9101, Nijmegen, 6500 HB, The Netherlands

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BMC Cancer 2013, 13:128  doi:10.1186/1471-2407-13-128

Published: 18 March 2013

Abstract

Background

αB-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 αB-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

αB-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 αB-crystallin expression. Additionally, the effects of αB-crystallin knockdown on VEGF secretion and cell motility were studied in vitro.

Results

Patients with higher staining fractions of αB-crystallin exhibited a significantly shorter MFS (Log-Rank test, p < 0.005). Under normoxic conditions αB-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 αB-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 αB-crystallin expression is associated with distant metastases formation in HNSCC patients. This association might relate to the chaperone function of αB-crystallin in mediating folding and secretion of VEGF and stimulating cell migration.

Keywords:
CRYAB protein; HspB5; Vascular endothelial growth factor A; Cell movement; Neoplasm metastasis; Carcinoma; Squamous cell of head and neck