Defined Localization of Nestin-expressing Cells in l-arginine-induced Acute Pancreatitis

Ishiwata, Toshiyuki; Kudo, Mitsuhiro; Onda, Munehiko; Fujii, Takenori; Teduka, Kiyoshi; Suzuki, Taeko; Korc, Murray; Naito, Zenya

doi:10.1097/01.mpa.0000220860.01120.21

Cited by 27 publications

(23 citation statements)

References 39 publications

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“…In vivo, Nestin is not present in endocrine cells during either embryogenesis or adulthood, underscoring the conclusion that endocrine cells do not derive from Nestin-expressing progenitors (7,8,(11)(12)(13)(14)(15). Moreover, in rodents, Nestin-expressing cells contribute to the regenerative capacity of the exocrine pancreas after partial pancreatectomy and during recovery from acute pancreatitis (15,16).…”

Section: Resultsmentioning

confidence: 76%

“…As shown in (Fig. 1 E-H Inasmuch as Nestin is up-regulated when acinar cell proliferation is induced in the pancreas (15,16) and is expressed in multiple cultured human pancreatic cancer cell lines (present work; data not shown), one could propose that Nestin expression is activated or up-regulated in the pancreas during transformation. Our following in vivo data strongly suggest that the initial oncogenic event occurs in Nestin-expressing cells.…”

Section: Resultsmentioning

confidence: 88%

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The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia

Carrière

Seeley

Goetze

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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120

108

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To determine the cell compartment in which initial oncogenic mutations occur in pancreatic ductal adenocarcinoma (PDAC), we generated a mouse model in which endogenous expression of mutated Kras (Kras G12D ) was initially directed to a population of pancreatic exocrine progenitors characterized by the expression of Nestin. Targeting of oncogenic Kras to such a restricted cell compartment was sufficient for the formation of pancreatic intraepithelial neoplasias (PanINs), putative precursors to PDAC. PanINs appeared with the same grade and frequency as observed when Kras G12D was targeted to the whole pancreas by a Pdx1-driven Cre recombinase strategy. Thus, the Nestin cell lineage is highly responsive to Kras oncogenic activation and may represent the elusive progenitor population in which PDAC arises.pancreatic ductal adenocarcinoma ͉ cell of origin ͉ Kras G12D

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Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 88%

The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia

Carrière

Seeley

Goetze

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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120

108

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“…Furthermore, the expression of intermediate filament Nestin is regulated by WT1 (93). The expression of Nestin is increased in regenerating tissue and is believed to participate in cellular remodeling and angiogenesis (94)(95)(96). Coexpression of WT1 and Nestin was found in the epicardium and endothelial cells of the embryonic heart in mice (93) and in vascular endothelium of patients who died after MI (97,98).…”

Section: The Role Of Wt1 In Endothelial Cellsmentioning

confidence: 89%

WT1 in Cardiac Development and Disease

2016

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The heart is essential for realizing the distribution of oxygen and nutrients throughout the body. Therefore, the heart is the first organ to develop and is already functional in its most primitive structure during embryogenesis. Recent studies indicate that the transcription factor Wilms' tumor-1 (WT1) is important for many aspects of cardiac development. WT1 expression is first observed in the proepicardium, a group of progenitor cells that give rise to a mesothelial sheet covering the heart, the epicardium. WT1 expression in epicardial cells is required for their epithelial-to-mesenchymal transformation forming epicardium-derived cells that will contribute to the formation of coronary vessels and interstitial fibroblasts. Endothelial cells within the heart also express WT1, whereas the endothelial cells in other Duim et al. 212 parts of the embryo do not. The endothelial expression of WT1 during cardiac development is likely to be important for vascular formation. After cardiac injury, WT1 is temporally upregulated in the epicardium and in the endothelial cells in the infarcted area and border zone, which points to a potential important role for WT1 in cardiac repair and regeneration. In this chapter, we describe the many faces of WT1 within the heart.

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“…16,17,21 Moreover, it has been recently demonstrated that activation of oncogenic K-ras in the nestin cell lineage is sufficient for the initiation of premalignant pancreatic intraepithelial neoplasia (PanIN) lesions in mice. 27 We have recently reported that nestin immunoreactivity was present in the cancer cells in approximately 30% of PDAC cases, and that nestin expression in pancreatic cancer cells correlated with nerve invasion and the presence of cancer cells at the tumor resection margins.…”

Section: Introductionmentioning

confidence: 99%

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

Matsuda

Naito

Kawahara

et al. 2011

Cancer Biology & Therapy

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Nestin, is a class VI intermediate filament (IF) that is expressed in 30% of pancreatic ductal adenocarcinoma (pDaC) cases, and its expression in pDaC positively correlates with peripancreatic invasion. an expression vector carrying a short hairpin RNa (shRNa) targeting nestin was stably transfected into paNC-1 and pK-45h human pancreatic cancer cells, which express high nestin levels. alterations in morphology and alignment of actin filaments and α-tubulin were examined by phase-contrast and immunocytochemistry. effects on cell growth, migration in scratch and Boyden chamber assays, invasion, cell adhesion, and in vivo growth were determined. Differences in mRNa levels were examined by arrays. Nestin shRNa-transfected cells exhibited decreased nestin expression, a sheet-like appearance with tight cellcell adhesion, increased expression of filamentous F-actin and e-cadherin, and attenuated migration and invasion, both of which were enhanced following nestin re-expression. expression of α-tubulin, and in vitro cell growth and adhesion were not altered by nestin downregulation, whereas hepatic metastases were decreased. Thus, nestin plays important roles in pancreatic cancer cell migration, invasion and metastasis by selectively modulating the expression of actin and cell adhesion molecules, and may therefore be a novel therapeutic target in pDaC.

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Defined Localization of Nestin-expressing Cells in l-arginine-induced Acute Pancreatitis

Abstract: Transient nestin expression occurs in specific cell types during the proliferative stage after recovery from L-arginine-induced pancreatitis and may represent the contribution of stem cells and/or progenitor cells to the regenerative capacity of the pancreas.

Cited by 27 publications

References 39 publications

The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia

The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia

WT1 in Cardiac Development and Disease

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

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