Extracellular Vesicles from Esophageal Squamous Cell Carcinoma Promote Angiogenesis and Tumor Growth

Angiogenesis is a prerequisite for tumor development and metastasis. Emerging evidence shows that tumor-derived extracellular vesicles (EVs) are an important component of tumor microenvironment, which participate in the communication between normal cells and tumor cells. In this study, we aimed to investigate the role of EVs derived from esophageal squamous cell carcinoma (ESCC) on tumor angiogenesis. We found that ESCC cell-derived EVs promoted the proliferation, migration, and tubule formation of human umbilical vein endothelial cells in vitro, and enhanced angiogenesis and tumor growth in vivo. Our results suggest that ESCC cell-derived EVs could promote angio-genesis and tumor growth, which also indicated the application of EVs as a valuable therapeutic strategy of ESCC.

cT1N0M0 Esophageal Squamous Cell Carcinoma Invades the Muscularis Mucosa or Submucosa: Comparison of the Results of Endoscopic Submucosal Dissection and Esophagectomy

Background: Endoscopic submucosal dissection (ESD) combined with selective adjuvant chemoradiotherapy may be a new treatment option for cT1N0M0 esophageal squamous cell carcinoma (ESCC) invading muscularis mucosa or submucosa (pT1a-M3/pT1b). We aim to report the effectiveness of this treatment by comparing the results of esophagectomy. Methods: This retrospective single-center study included 72 patients with pT1a-M3/pT1b ESCC who received ESD combined with selective adjuvant chemoradiotherapy (n = 40) and esophagectomy (n = 32). The main outcome comparison was overall survival (OS). The secondary outcomes were treatment-related events, including operation time, complication rate, and length of hospital stay. Disease-specific survival (DSS) and progression-free survival (PFS) were also evaluated. Results: There were no significant differences in the rates of OS, DSS, and PFS between the two groups (median follow-up time: 49.2 months vs. 50.9 months); these were also the same in the subgroup analysis of pT1b ESCC patients. In the ESD group, the procedure time, overall complication rates, and length of hospital stay were significantly reduced. However, the metachronous recurrence rate was significantly higher. In a multivariate analysis, tumor depth and R0 resection were the independent factors associated with OS. Conclusions: ESD combined with selective adjuvant chemoradiotherapy can be an alternative treatment to esophagectomy for cT1N0M0 ESCC invading muscularis mucosa or submucosa.

Preliminary study on the role and mechanism of KIRREL3 in the development of esophageal squamous cell carcinoma (ESCC)

Background: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive tract, which is very harmful to human health. The JAK-STAT signaling pathway is a recognized carcinogenic pathway that plays a role in the proliferation, apoptosis, migration, and invasion of a variety of cancer cells. Some studies have shown that the activation status of STAT3 affects the expression of KIRREL3. However, the expression of KIRREL3 in ESCC and its relationship with KIRREL3 or the JAK-STAT signaling pathway is still unclear.Methods: In this study, we used immunohistochemistry and western blotting to analyze the protein expression levels of KIRREL3 in tumor tissues and ESCC cell lines. We applied proliferation assays, plate clone formation assays, Transwell assays, flow cytometry analysis, and CDX animal models to examine the role of KIRREL3 in ESCC.Results: The results indicate that KIRREL3 is highly expressed to varying degrees in ESCC tissues and cell lines. Knocking down KIRREL3 expression in ESCC cells could correspondingly inhibit cell proliferation, colony formation, invasion, and migration, and had some effects on cell cycle progression and apoptosis. In addition, overexpressing KIRREL3 in these cells had opposite effects. Tumor formation in nude mice experiments also confirmed that KIRREL3 is involved in the growth of ESCC cells in vivo.Conclusions: These data suggest that KIRREL3 plays a key role in the development of ESCC, and KIRREL3 is a potential new target for the early diagnosis and clinical treatment of this disease.

Elevated FAM84B promotes cell proliferation via interacting with NPM1 in esophageal squamous cell carcinoma

Family with sequence similarity 84, member B (FAM84B) is a significant copy number amplification gene in the 8q24.21 locus identified by our previous WGS study in esophageal squamous cell carcinoma (ESCC). However, its clinical relevance and potential mechanisms have been elusive. Here, we performed the association analyses between FAM84BAmp and clinicopathological features using our dataset with 507 ESCC samples. The results indicated that, compared with the FAM84Bnon-Amp patients, the FAM84BAmp patients showed a more aggressive and a worse prognosis. Significant correlation was discovered between the expression level of FAM84B and FAM84BAmp in ESCC cohort. Furthermore, we found that the forced expression change of FAM84B can influence ESCC cell proliferation and cell cycle status, which is probably mediated by NPM1. A direct interaction between FAM84B and the C-terminal (189-294aa) of NPM1 was identified, which increased the NPM1 nuclear expression. Over-expression of NPM1 could inhibit the CDKN2A protein expression, which might affect the ESCC cell cycle. Our results indicate FAM84B CNA may be a potential diagnostic and therapeutic biomarker in ESCC, meanwhile, reveal a novel mechanism of FAM84B that it promotes tumorigenesis via interacting with NPM1 and suppressing CDKN2A.