Contribution of nestin positive esophageal squamous cancer cells on malignant proliferation, apoptosis, and poor prognosis.

Beilong Zhong,Andy Peng Xiang,Tao Wang,Weiqiang Li,Weilin Yang,Xueping Lun,Zhenguang Chen,Sannv Zheng,Jinli Zhang

doi:10.1186/1475-2867-14-57

Abstract

BackgroundThe stem cell-associated intermediate filament nestin has recently been linked with neoplastic transformation, but the specific mechanism by which nestin positive tumor cells leads to malignant invasion and metastasis behaviors of esophageal squamous cell carcinoma (ESCC) remains unclear.MethodsTo obtain insight into the biological role of nestin in ESCC, we explored the association of the nestin phenotype with malignant proliferation and apoptosis in esophageal squamous cancer cells. Nestin expression was determined in ESCC specimens and cell lines, and correlated with clinicopathological properties, including clinical prognosis and proliferative markers. The association of the nestin phenotype with apoptotic indicators was also analyzed.ResultsNestin was expressed in ESCC specimens and cell lines. ESCC patients with nestin-positive tumors had significantly shorter median survival and progression-free survival times than those with nestin-negative tumors. Positive staining for the proliferation markers Ki67 and PCNA (proliferating cell nuclear antigen) was detected in 56.9% and 60.2% of ESCC specimens, respectively, and was strongly correlated with the nestin phenotype. Notably, expression of cyclin dependent kinase-5 (CDK5) and P35 was detected in 53.8% and 48.4% of ESCC specimens, respectively, and was strongly associated with the nestin phenotype.ConclusionOur data demonstrated nestin expression in ESCC specimens and cell lines, and revealed a strong association of the nestin phenotype with poor prognosis in ESCC patients. Furthermore, we showed that nestin positive ESCC cells played an important role in the malignant proliferation and apoptosis.

Highlights

Esophageal cancer is a malignancy of the esophagus common throughout the world that is characterized by its high invasiveness and mortality
Recent reports have linked nestin with malignant characteristics in different cancers and suggested that abundant nestin positive cancer cells correlate with greater malignancy and poor prognosis [14,15,16,17]
Because no previous studies have provided detailed information on signaling mechanisms involved in the proliferation of esophageal cancer cells relevant to the nestin phenotype, we further investigated the mechanism underlying this linkage

Summary

Introduction

Esophageal cancer is a malignancy of the esophagus common throughout the world that is characterized by its high invasiveness and mortality. We previously demonstrated that the majority of tumor cells in non-small cell lung cancer samples are nestinpositive and showed that nestin expression was positively correlated with the subset of lung cancer patients displaying poor outcomes and high levels of proliferative markers [18,19]. The specific function of nestin positive tumor cells in the invasive and metastatic behaviors of esophageal cancer remains unclear. The precise mechanisms of nestin positive cancer cells action in the proliferation and metastasis of ESCC require further elucidation. The stem cell-associated intermediate filament nestin has recently been linked with neoplastic transformation, but the specific mechanism by which nestin positive tumor cells leads to malignant invasion and metastasis behaviors of esophageal squamous cell carcinoma (ESCC) remains unclear

Methods

Results

Conclusion