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

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.

Cyclin-Dependent Kinase 5 (CDK5) Controls Melanoma Cell Motility, Invasiveness, and Metastatic Spread—Identification of a Promising Novel therapeutic target

“…In a recent report, CDK5 expression and activation in approximately 50% of esophageal squamous cell carcinoma samples have been described and were linked to distinct subsets of tumors with adverse prognosis and enhanced expression of the stem cell marker nestin [40] .…”

Clinical significance of CD133 and Nestin in astrocytic tumor: The correlation with pathological grade and survival

“…For instances, overexpression of CD133 confers poor prognosis in invasive breast cancer, colorectal cancer, pancreatic cancer, etc . In addition, the negative impact of Nestin on survival has also been observed in lung cancer, esophageal squamous cancer, bladder cancer, etc . Whereas in astrocytic tumor, the tumor of the central nervous system, the effects of CD133 and Nestin on prognosis are only discovered in a small volume of literatures .…”

“…[21][22][23] In addition, the negative impact of Nestin on survival has also been observed in lung cancer, esophageal squamous cancer, bladder cancer, etc. [24][25][26] Whereas in astrocytic tumor, the tumor of the central nervous system, the effects of CD133 and Nestin on prognosis are only discovered in a small volume of literatures. 18,19 Therefore, this present study recruited relatively more patients with astrocytic tumor compared with the previous literatures and aimed to further validate the clinical relevance of CD133 and Nestin in astrocytic tumor regarding their impact on survival.…”

Expression of stem cell markers Nanog and Nestin in lip squamous cell carcinoma and actinic cheilitis

“…NANOG is a transcription factor present in embryonic stem cells and overexpressed during neoplastic development, and it plays a key role in the conservation of cell differentiation and proliferation both in the undifferentiated cells of OSCC and in CSCs (Watanabe et al, 2014). NESTIN, an intermediate filament protein, is related to aggressive behavior in pancreatic, lung, breast, and prostate cancer; it is considered to be an important prognostic factor, uncommitted to other clinical and pathological factors (Guérette, Khan, Savard, & Vincent, 2007;Mangiola et al, 2007;Matsuda, Kure, & Ishiwata, 2012;Ryuge et al, 2011;Zhong et al, 2014). β-tubulin is a cytoskeleton protein present in mesenchymal cells, and its expression in cancer cells may be related to epithelial-mesenchymal transition (EMT) (Huang et al, 2010;Onoue et al, 2006), a phenomenon that provides malignant cells with the biological characteristics required for invasion and metastasis, key steps of tumor progression (Li & Li, 2015).…”