Role of hypoxia-inducible factor-1α and CD146 in epidermal growth factor receptor-mediated angiogenesis in salivary gland adenoid cystic carcinoma

Abstract

Adenoid cystic carcinoma (AdCC) of the salivary gland in the head and neck is characterized by indolent yet persistent growth, multiple local recurrences and early hematogenous metastasis. Considering the possible association between the epidermal growth factor receptor (EGFR) signaling pathway and angiogenesis in various types of cancer and the overexpression of EGFR in AdCC, it is reasonable to examine the correlation between angiogenesis and the EGFR signaling pathway in this carcinoma. In the present study, the expression of EGFR, CD31, CD146 and hypoxia-inducible factor-1α (HIF-1α) were evaluated by immunohistochemical staining with tissue microarray containing normal salivary gland (NSG), pleomorphic adenoma (PMA) and AdCC tissues. Pearson's correlation coefficient was conducted to demonstrate the correlation between EGFR, CD31, CD146 and HIF-1α. To determine their similarity and intimacy, hierarchical analysis was performed with Cluster 3.0 and then visualized using TreeView software. Immunohistochemical results of tissue microarrays were quantified, revealing that the expression of EGFR, CD146 and HIF-1α increased in AdCC compared with in PMA and NSG tissues. The association between the expression of EGFR and CD31 was significant and positive. The expression of CD146 and HIF-1α was positively correlated with EGFR and CD31, respectively. These findings suggest that the EGFR signaling pathway has a vital role in AdCC progression and may be associated with HIF-1α-mediated angiogenesis. These results may enhance our understanding of the mechanism underlying AdCC progression and provide potential clinical therapeutic strategies based on the inhibition of EGFR.

CD146-HIF-1α hypoxic reprogramming drives vascular remodeling and pulmonary arterial hypertension

“…Notably, the apparent functional role of CD146 in vascular diseases, such as atherosclerosis 20 , multiple sclerosis 21 , systemic sclerosis 22 , and cancer 23 , is dependent on its capacity in promoting cell proliferation, inflammation and fibrosis, the prominent hallmarks of PAH. Moreover, studies in vascular cells suggested that a possible link exists between CD146 expression and HIF-1α activation 24–26 . Given such close association of CD146 with PAH features and the broad impact of CD146 in vascular disorders, we aimed to determine the connection between CD146 and HIF-1α in vascular remodeling, and to further explore its potential as an anti-remodeling target for PAH therapy.…”

Experimental study on TGF‐β1‐mediated CD147 expression in oral submucous fibrosis

“…The immunohistochemical (IHC) methods used have been previously described in detail (Wang, Zhao, Zhang, et al., ). Briefly, all sections were performed antigen retrieval in sodium citrate by microwave heating.…”

“…All the slides were scanned using an Aperio ScanScope CS whole slide scanner (Vista, CA, USA) with background subtraction. Positive results were quantified using Aperio Quantification software (Version 9.1) for membrane, nuclear, or pixel quantification, and the histoscore was calculated using a formula as previously described (Wang, Zhao, Zhang, et al., ).…”

HIF-1α and mTOR – Possible Novel Strategies of Targeted Therapies in p16-positive and -negative HNSCC

“…In HNSCC, EGFR mediated signalling is important for angiogenesis through HIF-1α and translocation-associated Notch homolog 1 (Notch1) (55). We found that the expression of HIF-1α was decreased by all tested substances in p16-negative HNSCC with one exception for dasatinib after 24 h. Wang and colleagues demonstrated that EGFR expression is correlated with a higher HIF-1α expression in adenoid cystic carcinoma cells of the salivary gland in head and neck (56). Our findings are consistent with this observation as EGFR inhibitors erlotinib and gefitinib significantly reduced HIF-1α levels in p16-negative cancer cells.…”