Chemokines and their receptors as biomarkers in esophageal cancer
ESOPHAGUS
Authors: Goto, Masakazu; Liu, Mingyao
Abstract
Esophageal cancer (EC) is one of the most lethal malignancies of the digestive tract and remains to be improved poor prognosis. Two histological subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), are major characteristics of EC. Deep understanding about both subtypes is essential to overcome EC. Here, we focus on chemokines and their receptors as biomarkers and their current applications for the prognosis in EC. We reviewed relevant articles identified using PubMed database for the chemokines and their receptors in EC analyzed by immunohistochemistry. The primary objective is to summarize evidences for them as prognostic biomarkers in EC. A total of twenty-one articles were reviewed after exclusion. Most studies have been done in ESCC, and less in EAC. CXCL12 and its receptor CXCR4 have been shown in both subtypes as biomarkers. CXCR7, CXCL8 and its receptor CXCR2, and CCL21 and its receptor CCR7 have been examined in ESCC. Although it was a small number of reports, CXCL10, CCL4, and CCL5 have been indicated to have anti-tumor effects in ESCC. Chemokines and their receptors have the potential to be the biomarkers in EC. Comparative studies between ESCC and EAC will reveal the similarity and difference in these two subtypes of EC. These studies may indicate whether these molecules play important roles in both subtypes or are unique to one or another.
AIRE is induced in oral squamous cell carcinoma and promotes cancer gene expression
PLOS ONE
Authors: Chi Thi Kim Nguyen; Sawangarun, Wanlada; Mandasari, Masita; Morita, Kei-ichi; Harada, Hiroyuki; Kayamori, Kou; Yamaguchi, Akira; Sakamoto, Kei
Abstract
Autoimmune regulator (AIRE) is a transcriptional regulator that is primarily expressed in medullary epithelial cells, where it induces tissue-specific antigen expression. Under pathological conditions, AIRE expression is induced in epidermal cells and promotes skin tumor development. This study aimed to clarify the role of AIRE in the pathogenesis of oral squamous cell carcinoma (OSCC). AIRE expression was evaluated in six OSCC cell lines and in OSCC tissue specimens. Expression of STAT1, ICAM1, CXCL10, CXCL11, and MMP9 was elevated in 293A cells stably expressing AIRE, and conversely, was decreased in AIRE-knockout HSC3 OSCC cells when compared to the respective controls. Upregulation of STAT1, and ICAM in OSCC cells was confirmed in tissue specimens by immunohistochemistry. We provide evidence that AIRE exerts transcriptional control in cooperation with ETS1. Expression of STAT1, ICAM1, CXCL10, CXCL11, and MMP9 was increased in 293A cells upon Ets1 transfection, and coexpression of AIRE further increased the expression of these proteins. AIRE coprecipitated with ETS1 in a modified immunoprecipitation assay using formaldehyde crosslinking. Chromatin immunoprecipitation and quantitative PCR analysis revealed that promoter fragments of STAT1, ICAM1, CXCL10, and MMP9 were enriched in the AIRE precipitates. These results indicate that AIRE is induced in OSCC and supports cancer-related gene expression in cooperation with ETS1. This is a novel function of AIRE in extrathymic tissues under the pathological condition.