The epithelial-mesenchymal transition (EMT) plays a critical role in embryonic development. EMT is also involved in cancer progression and metastasis and it is probable that a common molecular mechanism is shared by these processes. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. Furthermore, the acquisition of EMT features has been associated with chemoresistance which could give rise to recurrence and metastasis after standard chemotherapeutic treatment. Thus, EMT could be closely involved in carcinogenesis, invasion, metastasis, recurrence, and chemoresistance. Research into EMT and its role in cancer pathogenesis has progressed rapidly and it is now hypothesized that novel concepts such as cancer stem cells and microRNA could be involved in EMT. However, the involvement of EMT varies greatly among cancer types, and much remains to be learned. In this review, we present recent findings regarding the involvement of EMT in cancer progression and metastasis and provide a perspective from clinical and translational viewpoints. (Cancer Sci 2010; 101: 293-299) D evelopment of distant metastases is the final stage of solid cancer progression and is responsible for the majority of cancer-related deaths.(1) Distant metastasis alone or with concurrent locoregional recurrence accounts for nearly 80% of all first relapses in women with breast cancer.(2) While clinically of great importance, the biology of metastasis remains unsolved. The process of tumor metastasis consists of multiple steps, all of which are required to achieve tumor spreading.(3,4) First, cancer cells escape from the primary tumor site. Next, cancer cells invade the tumor stroma and enter the blood circulation directly or the lymphatic system via intravasation. Most circulating cancer cells undergo apoptosis due to anoikis conditions.(5) If cancer cells survive in circulation they may reach more suitable sites by attaching to endothelial cells and extravasating from the circulation into the surrounding tissues. Finally, distal colonization requires that cancer cells invade and grow in the new environment.Recently, the concept of the epithelial-mesenchymal transition (EMT), as developed in the field of embryology, has been extended to cancer progression and metastasis.(6,7) In vitro and experimental animal model data now support the role of EMT in metastasis, concepts supported by analyses of clinical samples. Indeed, the biology of EMT has been clarified in tumor samples through use of EMT-associated markers, such as mesenchymalspecific markers (i.e. vimentin and fibronectin), (8,9) epithelial specific markers (i.e. E-cadherin and cytokeratin), (10,11) and transcription factors (i.e. SNAIL and SLUG). (12) Most recently, several intriguing studies have described the novel mechanism underlying EMT activation. In the current study, we will discuss the role of small non-coding RNA (micro-RNA) in regulating EMT-r...

BACKGROUND: Exosomes are 40-nm to 100-nm membrane vesicles that are secreted by various cells, and they play a major role in cell-cell communication. The objective of this study was to clarify the significance of the levels of microRNA in exosomes extracted from the sera of patients with esophageal squamous cell cancer (ESCC). METHODS: The authors isolated exosomes in serum samples from patients who had ESCC and from patients who had benign diseases without systemic inflammation. Total RNA was purified from the exosomes, and expression levels of microRNA-21 (miR-21) were analyzed by quantitative real-time polymerase chain reaction. RESULTS: Serum exosomes from patients with ESCC induced the proliferation of ESCC cells in vitro. The expression levels of exosomal miR-21 were significantly higher in patients with ESCC than those with benign diseases with and without (C-reactive protein <0.3 mg/dL) systemic inflammation. MiR-21 was not detected in serum that remained after exosome extraction. Exosomal miR-21 expression was correlated with advanced tumor classification, positive lymph node status, and the presence of metastasis with inflammation or and clinical stage without inflammation (C-reactive protein <0.3 mg/dL). CONCLUSIONS: The current results confirmed that exosomal miR-21 expression is up-regulated in serum from patients with ESCC versus serum from patients who have benign diseases without systemic inflammation. Exosomal miR-21 was positively correlated with tumor progression and aggressiveness, suggesting that it may be a useful target for cancer therapy.

F. nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. F. nucleatum might also contribute to aggressive tumor behavior through activation of chemokines, such as CCL20. Clin Cancer Res; 22(22); 5574-81. ©2016 AACR.

Objective: To determine whether prognostic nutritional index (PNI) affects clinical outcome through local immunity in esophageal cancers. Background: PNI is an indicator of nutritional status and systemic immune competence, and has attracted attention as a prognostic biomarker. Tumor-infiltrating lymphocytes (TILs) are a specific histological feature of human cancers, reflecting an individual's immunological tumor response. Methods: Using a nonbiased database of 337 curatively resected esophageal cancers, we evaluated the relationship between PNI, TILs status, CD8 expression by immunohistochemical staining, and clinical outcome. Results: Compared with PNI-high cases (n = 220), PNI-low cases (n = 117) showed significantly worse overall survival (log-rank P < 0.001; hazard ratio: 2.23; 95% confidence interval: 1.56–3.18; P < 0.001; multivariate hazard ratio: 1.67; 95% confidence interval: 1.14–2.44; P = 0.008). The TILs status was also significantly correlated with overall survival (P < 0.001). In addition, PNI was significantly associated with TILs status (P < 0.001) and the CD8-positive cell count (P = 0.041). A significant relationship between the peripheral blood lymphocyte count and TILs status was also observed (P < 0.001). Conclusions: PNI and TILs score expression were associated with clinical outcome in esophageal cancer, supporting their roles as prognostic biomarkers. Considering the relationship between PNI and TILs, nutritional status and systemic immune competence may influence patient prognosis through local immune response.