New insights into pancreatic cancer stem cells

Rao, Chinthalapally V.; Mohammed, Altaf

doi:10.4252/wjsc.v7.i3.547

Cited by 52 publications

(58 citation statements)

References 92 publications

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“…Moreover, CSCs remain quiescent and also exhibit an enhancement of their DNA repair capacity, as well as abnormally activated developmental signaling cascades and anti-apoptotic pathways 4–7 .…”

Section: Discussionmentioning

confidence: 99%

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PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

Kumazoe

Takai

Hiroi

et al. 2017

Sci Rep

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Recurrence following chemotherapy is observed in the majority of patients with pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that cancer stem cells (CSCs) may be involved in PDAC recurrence and metastasis. However, an efficient approach to targeting pancreatic CSCs remains to be established. Here we show that in cancer cells overexpressing the 67-kDa laminin receptor (67LR)-dependent cyclic GMP (cGMP) inducer, epigallocatechin-3-O-gallate (EGCG) and a phosphodiesterase 3 (PDE3) inhibitor in combination significantly suppressed the Forkhead box O3 and CD44 axis, which is indispensable for the CSC properties of PDAC. We confirmed that the EGCG and PDE3 inhibitor in combination strongly suppressed tumour formation and liver metastasis in vivo. We also found that a synthesized EGCG analog capable of inducing strong cGMP production drastically suppressed the CSC properties of PDAC and extended the survival period in vivo. In conclusion, the combination treatment of EGCG and a PDE3 inhibitor as a strong cGMP inducer could be a potential treatment candidate for the eradication of CSCs of PDAC.

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Section: Discussionmentioning

confidence: 99%

“…However, the five-year survival rate has not changed by more than approximately 5% during the past 40 years and the majority of patients (approximately 95%) experience a recurrence following chemotherapy 4 . Considering these situation, the establishment of a novel therapeutic strategy is particular importance.…”

Section: Introductionmentioning

confidence: 99%

PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

Kumazoe

Takai

Hiroi

et al. 2017

Sci Rep

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“…Besides CD24, CD44, CD133, and ESA, there are several other common stem cell markers have been identified as CSCs-specific markers in a variety of CSCs subpopulations, such as aldehyde dehydrogenase 1 (ALDH1), another cell surface marker, and myc-related translation/localization regulatory factor (c-Myc), homeobox protein (Nanog), sex determining region Y-box 2 (Sox-2) and octamer-binding transcription factor 4 (Oct-4), which are typical transcription factors regulating the self-renewal capacity of CSCs [14]. To determine whether the spheroids have acquired stem cell-like features, the spheroids were characterized of their expression levels of the above CSCs markers by qRT-PCR, western blotting and immunofluorescence staining.…”

Section: Panc-1 Spheroid Cells Express Markers For Maintaining the Csmentioning

confidence: 99%

Transcriptome Profiling of Panc-1 Spheroid Cells with Pancreatic Cancer Stem Cells Properties Cultured by a Novel 3D Semi-Solid System

Yang¹,

Zhang²,

Tang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Pancreatic cancer remains one of the deadliest human malignancies, the lethality of which may be attributed to the presence of pancreatic cancer stem cells (PCSCs), a small subpopulation of cells existing within pancreatic tumor with high carcinogenesis. Therefore, it is crucial to establish an efficient enrichment and culture system of PCSCs and identify the key genes involved in the regulation of PCSCs. The three-dimensional (3D) liquid suspension mammosphere culture system has been established for enrichment and culture of PCSCs in vitro as the cell spheres are likely to originate from individual cell clone, but it has been challenged because the cell spheroids could be a result of cell aggregation. Methods: We optimized the existing culture system by adding methylcellulose to create a 3D semi-solid system which prevented the non-specific aggregation. Then we identified the CSC properties of Panc-1 spheroid cells cultured by this system by detecting the genes associated with stemness and by evaluation of the tumorigenicity in vitro and in vivo through invasion, migration and xenograft experiments methods. Subsequently, we performed high-throughput sequencing (HTS) of the Panc-1 spheroid cells. Results: We confirmed the PCSCs properties and high malignancy of the Panc-1 spheroid cells enriched by our novel 3D semi-solid system both in vitro and in vivo. Hundreds of mRNA, microRNA (miRNA) and dozens of long non-coding RNA (LncRNA) were identified to be differentially regulated in PCSCs-like Panc-1 spheroid cells compared with their parental cells by HTS. Conclusions: Our results demonstrate an efficient enrichment and culture system for Panc-1 spheroid cells with the PCSCs properties. The differentially expressed genes and their targets identified by the HTS of the Panc-1 spheroid cells can serve as new potential biomarkers for pancreatic cancer diagnosis and targeted therapy.

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“…Cancer stem cells are thought to be the driving force of cancer initiation, progression, metastasis and drug resistance and are among current targets of pancreatic cancer therapy [48, 49]. The stem cell biomarkers CD133, ALDH-1 as well as SHH and its downstream effector Gli-1 are involved in cancer stem cell self-renewal, clonogenicity, tumorigenicity, metastasis and drug resistance of numerous solid cancers, including PDAC [36–38, 50].…”

Section: Discussionmentioning

confidence: 99%

Prevention of pancreatic cancer in a hamster model by cAMP decrease

et al. 2016

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Smoking and alcoholism are risk factors for the development of pancreatitis-associated pancreatic ductal adenocarcinoma (PDAC). We have previously shown that these cancers overexpressed stress neurotransmitters and cyclic adenosine monophosphate (cAMP) while the inhibitory neurotransmitter γ-aminobutyric acid (GABA) was suppressed. Using a hamster model, the current study has tested the hypothesis that cAMP decrease by GABA supplementation in the drinking water prevents the development of pancreatitis-associated PDAC. Our data reveal strong preventive effects of GABA supplementation on the development of PDAC and pancreatic intraductal neoplasia (PanIN). ELISA assays and immunohistochemistry revealed significant decreases in the levels of cAMP and interleukin 6 accompanied by reductions in the expression of several cancer stem cell markers and phosphorylated signaling proteins, which stimulate cell proliferation, and migration in pancreatic exocrine cells of GABA treated animals. We conclude that cAMP decrease by GABA supplementation inhibits multiple cancer stimulating pathways in cancer stem cells, differentiated cancer cells and the immune system, identifying this approach as promising novel tool for the prevention of PDAC in individuals with a history of smoking and alcoholism.

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New insights into pancreatic cancer stem cells

Cited by 52 publications

References 92 publications

PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

Transcriptome Profiling of Panc-1 Spheroid Cells with Pancreatic Cancer Stem Cells Properties Cultured by a Novel 3D Semi-Solid System

Prevention of pancreatic cancer in a hamster model by cAMP decrease

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