Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis

Matsuda, Yoko; Naito, Zenya; Kawahara, Kiyoko; Nakazawa, Naoki; Korc, Murray; Ishiwata, Toshiyuki

doi:10.4161/cbt.11.5.14673

Cited by 87 publications

(104 citation statements)

References 49 publications

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“…These features are cellular mechanisms underlying cancer progression and metastasis, and they are also common characteristics found in ATC cells. Recent basic research demonstrated that nestin regulates actin and cell adhesion molecules affecting migration, invasion and metastasis (25). In the present study, however, there were no significant correlations between the expression of nestin in the tumour and the clinicopathological characteristics of the patients, indicating that nestin did not accelerate disease progression in ATC.…”

Section: Univariate Analysis Multivariate Analysis ------------------contrasting

confidence: 53%

Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer

et al. 2015

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Abstract. The protein nestin, a neuronal stem cell marker, has been reported to indicate a poor prognosis in various tumours. Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its molecular background has not been identified. The present study evaluated the expression of nestin and its significance in ATC. Tissue samples from 23 patients with ATC were subjected to immunohistochemical staining and the staining intensity of nestin in the cytoplasm was evaluated. The expression of nestin in the tumour cytoplasm was confirmed in 6 of the 23 tissue samples (26.1%). Between the nestin-positive group (n=6) and the nestin-negative group (n=17), there were no significant differences in the clinicopathological factors of the patients. However, the nestin-positive group exhibited significantly worse prognoses than the nestin-negative group (median survival time, 86.5 vs. 306 days; P<0.01, log-rank test). The multivariate analysis indicated that nestin expression was a prognostic indicator for the ATC patients (hazard ratio, 5.59; 95% confidence interval, 1.63-19.50; P<0.01), which is independent of the known clinical indicators. Nestin expression has the potential to be an independent indicator of a poor prognosis for patients with ATC.

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Section: Univariate Analysis Multivariate Analysis ------------------contrasting

confidence: 53%

Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer

et al. 2015

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“…Furthermore, expression of nestin in PDAC cells was detected in approximately 30% of PDAC cases (22). Recently, we have reported that reduced expression level of nestin in PDAC cells attenuated migration, invasion and metastasis (59). Therefore, nestin may become a new molecular target for both PDAC cells and tumor angiogenesis for nestin-expressing PDAC cases.…”

Section: Discussionmentioning

confidence: 99%

Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis

Yamahatsu

Matsuda²,

Ishiwata

et al. 2012

Int J Oncol

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Abstract. The class VI intermediate filament protein, nestin is reported to be a progenitor cell marker in various tissues. In the present study, we analyzed the expression and roles of nestin in angiogenesis of pancreatic ductal adenocarcinomas, and determined whether nestin is a potential target for inhibiting tumor angiogenesis using a gene silencing strategy. Nestin expression was detected only in small vessels, whereas CD34, CD31 and factor VIII were also expressed in large-sized blood vessels in PDAC. The number of nestin-positive vessels was approximately 20% the number of CD34-positive vessels, and the average dimension of nestin-positive vessels was approximately 75% that of CD34-positive vessels. The PCNA labeling indices of nestin-positive vessels were higher than those of CD34-positive vessels and nestin-negative vessels. Reducing nestin expression by use of siRNA targeting nestin transcripts inhibited growth of the vascular endothelial cell lines, but there was no difference in cell motility. In xenograft models, administration of siRNA targeting mouse-nestin suppressed subcutaneous human pancreatic cancer cell growth in nude mice. In conclusion, nestin was expressed in small proliferating blood vessels in pancreatic cancer tissues and may be a useful marker of angiogenesis in pancreatic ductal adenocarcinoma tissues. Furthermore, nestin is a potential novel therapeutic target in pancreatic cancers to inhibit tumor angiogenesis.

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“…Although our study presents nestin as an inhibitor of invasion, some studies indicate that nestin is a positive regulator of migration and metastasis (Ishiwata et al, 2011b;Kleeberger et al, 2007;Matsuda et al, 2011). Nestin might have contrasting effects on cell function depending on the cell type and transformation stage.…”

Section: Discussionmentioning

confidence: 99%

Nestin regulates prostate cancer cell invasion by influencing FAK and integrin localisation and functions

Hyder

Lazaro

Pylvänäinen

et al. 2014

Journal of Cell Science

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BSTRACTNestin, an intermediate filament protein and marker of undifferentiated cells, is expressed in several cancers. Nestin is important for neuronal survival and is a regulator of myogenesis but its function in malignancy is ambiguous. We show that nestin downregulation leads to a redistribution of phosphorylated focal adhesion kinase (pFAK, also known as PTK2) to focal adhesions and alterations in focal adhesion turnover. Nestin downregulation also leads to an increase in the protein levels of integrin a5b1 at the cell membrane, activation of integrin b1 and an increase in integrin clustering. These effects have striking consequences for cell invasion, as nestin downregulation leads to a significant increase in pFAK-and integrin-dependent matrix degradation and cell invasion. Our results indicate that nestin regulates the localisation and functions of FAK and integrin. Because nestin has been shown to be prevalent in a number of specific cancers, our observations have broad ramifications for the roles of nestin in malignant transformation.

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Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis

Cited by 87 publications

References 49 publications

Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer

Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer

Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis

Nestin regulates prostate cancer cell invasion by influencing FAK and integrin localisation and functions

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