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

Abstract

BackgroundαB-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).MethodsαB-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.ResultsPatients 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.ConclusionsOur 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.

Alpha B‐crystallin promotes the invasion and metastasis of gastric cancer via NF‐κB‐induced epithelial‐mesenchymal transition

“…For example, Shi et al8 found that CRYAB promoted the invasion and metastasis of colorectal cancer cells via EMT. Consistently, Chantal et al suggested CRYAB as a useful biomarker to help fine‐tune treatment in head and neck squamous cell carcinoma, possibly by targeting CRYAB‐mediated cell motility 9. Obviously, these findings provide evidence delineating the pivotal role of CRYAB in cancer invasion and metastasis.…”

“…Interestingly, recent studies have revealed that CRYAB is aberrantly overexpressed in various types of cancer, and its expression could promote cell invasion and metastasis 8, 9, 10. For example, Shi et al8 found that CRYAB promoted the invasion and metastasis of colorectal cancer cells via EMT.…”

Squamous cell carcinoma of the oral cavity and circulating tumour cells

“…The role of the expression rates of integrin alpha-3 for locoregional and ITGB4 for haematogenous dissemination and, therefore, cancer cell motility and anchorage-independent survival, which are vital for OSCC recurrence and metastasis, has previously been shown. Furthermore, the importance of integrin beta1 in HNSCC and stimulated vascular endothelial growth factor secretion by alphaB-crystallin in HNSCC was specified [100,101] . In addition to these considerations, there might be a spread of tumour-derived molecules on a subcellular level, such as micro-RNAs.…”

Role of Small Heat Shock Protein HspB5 in Cancer

“…Overexpression of HspB5 can transform immortalized human mammary epithelial cells that can develop invasive mammary carcinomas in nude mice with basal-like breast tumor features (Moyano et al 2006 ). Consequently HspB5 can be considered as a biomarker in the diagnosis of breast cancers, especially in those with advanced grade (Ivanov et al 2008 ;Sitterding et al 2008 ;Tsang et al 2012 ). Similarly, high levels of HspB5 are associated with low survival rate in hepatocellular carcinoma (Huang et al 2013 ;Tang et al 2009 ), ovarian carcinoma (Volkmann et al 2013 ), clear cell renal cell carcinoma (Ho et al 2013 ) and head and neck squamous cell carcinoma (van de Schootbrugge et al 2013 ).…”