Nestin regulates epithelial-mesenchymal transition marker expression in pancreatic ductal adenocarcinoma cell lines

Abstract

Abstract. Nestin, a class VI intermediate filament, is a neuronal stem/progenitor cell marker that is also expressed by various types of cancer, including pancreatic ductal adenocarcinoma (PDAC). We previously detected nestin expression in approximately 30% of PDAC cases, and found that nestin promotes the migration, invasion and metastasis of cells. Findings of recent studies have shown that epithelial mesenchymal transition (EMT) is important in the invasion and migration of cancer. In the present study, we investigated whether an altered nestin expression affected the expression levels of EMT markers in PDAC cells. Two human PDAC cell lines, PK-45H and KLM-1, in which nestin was suppressed and overexpressed, respectively, were used. The expression levels of the EMT-related molecules E-cadherin, Snail, Slug and Twist were analyzed using quantitative RT-PCR. Results showed that E-cadherin expression was decreased in nestin-overexpressed KLM-1 cells, and increased in nestin-suppressed PK-45H cells. Snail gene expression in the PDAC cells was altered concomitantly with the changes in nestin expression, while the Slug gene expression was significantly decreased in nestin-overexpressed KLM-1 cells. The Twist gene expression was below the detection limit in the two PDAC cell lines. The present findings indicated that nestin may be involved in the control of cancer behaviors in PDAC via the modulation of EMT-related molecules.

Nestin phosphorylation at threonines 315 and 1299 correlates with proliferation and metastasis of human pancreatic cancer

“…Nestin regulates stemness, cell growth, and invasion in glioblastoma cells through the alteration of HSC71 . However, the effect of nestin on pancreatic cancer cell proliferation remains controversial . We previously found that inhibiting nestin expression by short hairpin RNA (shRNA) suppressed growth of the glioblastoma cell line A172, the melanoma cell line A375, and the lung cancer cell line H1975 .…”

“…Nestin phosphorylation affects several pancreatic cancer cell behaviors including cell growth, migration, invasion, and metastasis. Data from the present study and our previous studies indicate that nestin is a key factor in pancreatic cancer invasion and metastasis, and inhibition of nestin expression or phosphorylation may be a novel therapeutic strategy for treating pancreatic cancer.…”

“…We previously reported that nestin is highly expressed in 30% of human pancreatic cancer samples, and that nestin inhibition reduces cell migration and invasion abilities in vitro and liver metastasis in vivo . Furthermore, the metastatic potential of human pancreatic cancer cells correlates with stemness, and the epithelial mesenchymal transition is dependent on nestin expression . Together, these results indicate that nestin is a possible therapeutic target for pancreatic cancer treatment.…”

Endothelial and Epithelial Cell Transition to a Mesenchymal Phenotype Was Delineated by Nestin Expression

“…In the lungs of hypobaric hypoxic rats, numerous epithelial cells apparently underwent type II EMT depicted by the co‐expression of E‐cadherin and collagen type I (Kage & Borok, ; Yang et al, ; Pain et al, ). In type III EMT, nestin expression was identified as a novel phenotype required for proliferation and metastasis and a similar paradigm may be prevalent during Type II EMT (Ishiwata et al, ; Hagio et al, ; Matsuda et al, ). The removal of FBS led to the acquisition a mesenchymal phenotype by a subpopulation of primary passage adult rat alveolar epithelial cells depicted by the downregulation of E‐cadherin and concomitant induction of collagen type I.…”

“…Several studies have reported that nestin expression in renal‐ and lung‐derived resident stromal cells was upregulated following exposure to TGF‐β (Sakairi et al, ; Chabot et al, ). Nestin was also induced during Type III EMT and implicated in the acquisition of a proliferative and metastatic phenotype (Ishiwata et al, ; Hagio et al, ; Matsuda et al, ). Thus, it is tempting to speculate that one or more of the identified paradigms implicated in the appearance of pulmonary fibroblasts may be characterized by nestin expression.…”