WJZ carried out the transfection. LZS and LY performed the statistical analysis. HX participated in the design of the study. ZKX conceived of the study, and participated in its design and coordination. All authors read and approved the final manuscript.”
“Background Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive and invasive malignancies in the world. Despite combined modality approaches, the

prognosis in cases of ESCC remains extremely poor; patients exhibit a low 5-year survival rate, with the majority of cancer-related deaths resulting from metastatic spread of tumor cells [1]. Clinical observations have shown that lymph node involvement click here appears as one of the earliest features of ESCC [2]. Some abnormal molecular biology changes, such as tumor-induced lymphangiogenesis, are also considered to play a central role in the migration and metastatic spread of ESCC to lymph nodes. For example, high expression of vascular endothelial growth factor (VEGF)-C and the presence of newly developed lymphatic ducts was found to be the main avenue for dissemination of malignant cells to lymph ABT-263 supplier nodes in ESCC [3–5]. Lymphangiogenesis

is associated with neoplastic progression in the esophageal mucosa, and there is an increase in VEGF-C expression in Barrett’s epithelium as it progresses through dysplasia to esophageal carcinoma [6]. Moreover, lymphangiogenesis has been shown to correlate with the depth of malignant invasion, tumor stage, lymphatic and venous invasion, and lymph node metastasis Phloretin in esophageal cancer [7]. However, although several positive and negative regulators, including angiopoietins [8], neuropilin-2 [9], and COX-2 [10], are believed to contribute to the robust production of VEGF-C, the molecular regulatory

mechanisms involved in tumor-induced lymphangiogenesis of ESCC have remained unclear. One potential candidate is nuclear factor-κB (NF-κB), a sequence-specific transcription factor that responds to cellular signaling pathways involved in cell survival and resistance to chemotherapy; notably, aberrant NF-κB activation has been associated with some malignancies [11–13]. Although abnormities of NF-κB signaling have been reported to play an important role in carcinogenesis by promoting tumor-induced angiogenesis and neoplastic proliferation [14], the association of NF-κB with lymphangiogenesis in ESCC is less clear. Members of the Notch family of cell surface receptors and their ligands also warrant attention based on their role in vasculogenesis and their potential to act as oncogenes in the pathogenesis of certain carcinomas. These highly conserved proteins regulate “”decisions”" involved in cell-fate determination, including those involved in mammalian vascular development [15].