Pancreatic cancer stem cells: New insight into a stubborn disease

Zhan, Hanxiang; Xu, Jianwei; Wu, Dong; Zhang, Taiping; Hu, Sanyuan

doi:10.1016/j.canlet.2014.12.004

Cited by 68 publications

(54 citation statements)

References 108 publications

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“…However, others have highlighted that pancreatic cancer stem cells may express other/additional receptors and/or markers on their surface, such as CD133, PANC-1, CXCR4 (the receptor for chemoattractant stromal-derived factor-1 [SDF-1]), and c-Met (the tyrosine kinase receptor for hepatocyte growth factor [HGF]), as well as intracellular molecules like aldehyde dehydrogenase-1. Taken together, these findings suggest that, at different molecular levels, biological factors protect these cells from death induced by chemotherapeutic agents and enable their (almost unlimited) proliferation and survival [3][4][5][6][7][8][9][10][11][12][13][14].…”

Section: Concept Of Cancer (Stem) Cellsmentioning

confidence: 99%

“…According to experimental studies, among the several types of cancer cells that are present within the pancreatic tumor microenvironment, only a very small proportion (,1%) possesses the unique molecular armament necessary for tumor initiation and metastasis. This cell population is generally termed "pancreatic cancer stem cells" and is believed to be atop the hierarchy of all cancer (stem) cells [3][4][5][6][7]. In pancreatic adenocarcinoma, the probable molecular characteristics of this cell population has already been proposed.…”

Section: Concept Of Cancer (Stem) Cellsmentioning

confidence: 99%

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Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells

Błogowski

Bodnarczuk²,

Starzyńska

2016

Stem Cells Translational Medicine

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Pancreatic adenocarcinoma remains one of the most challenging diseases of modern gastroenterology, and, even though considerable effort has been put into understanding its pathogenesis, the exact molecular mechanisms underlying the development and/or systemic progression of this malignancy still remain unclear. Recently, much attention has been paid to the potential role of bone marrowderived stem cells (BMSCs) in this malignancy. Hence, herein, we comprehensively review the most recent discoveries and current achievements and concepts in this field. Specifically, we discuss the significance of identifying pancreatic cancer stem cells and novel therapeutic approaches involving molecular interference of their metabolism. We also describe advances in the current understanding of the biochemical and molecular mechanisms responsible for BMSC mobilization during pancreatic cancer development and systemic spread. Finally, we summarize experimental, translational, and/or clinical evidence regarding the contribution of bone marrow-derived mesenchymal stem cells, endothelial progenitor cells, hematopoietic stem/progenitor cells, and pancreatic stellate cells in pancreatic cancer development/progression. We also present their potential therapeutic value for the treatment of this deadly malignancy in humans. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:938-945 SIGNIFICANCE Different bone marrow-derived stem cell populations contribute to the development and/or progression of pancreatic cancer, and they might also be a promising "weapon" that can be used for anticancer treatments in humans. Even though the exact role of these stem cells in pancreatic cancer development and/or progression in humans still remains unclear, this concept continues to drive a completely novel scientific avenue in pancreatic cancer research and gives rise to innovative ideas regarding novel therapeutic modalities that can be safely offered to patients.

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Section: Concept Of Cancer (Stem) Cellsmentioning

confidence: 99%

Section: Concept Of Cancer (Stem) Cellsmentioning

confidence: 99%

Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells

Błogowski

Bodnarczuk²,

Starzyńska

2016

Stem Cells Translational Medicine

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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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“…Recent research in the field has shown that the enrichment of cancer stem cells depends on the microenvironment niches 54 In pancreatic cancer, in addition to regulating altered metabolism in order to combat hypoxic stress in the tumor, HIF1A also regulates stemness in the tumor microenvironment by upregulating self-renewal genes in the tumor 6, 55–57 . Thus, the hypoxic niche in the tumor microenvironment is one of the major driving forces for the tumor initiating population within it.…”

Section: Microenvironment Niches Promote Stemness and Chemoresistancementioning

confidence: 99%

Microenvironment in determining chemo-resistance in pancreatic cancer: Neighborhood matters

et al. 2017

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Every year, nearly 300,000 people are diagnosed with pancreatic cancer worldwide, and an equivalent number succumb to this disease. One of the major challenges of pancreatic cancer that contributes to its poor survival rates is the development of resistance to the standard chemotherapy. Heterogeneity of the tumor, the dense fibroblastic stroma, and the aggressive biology of the tumor all contribute to the chemoresistant phenotype. In addition, the acellular components of the tumor microenvironment like hypoxia, stress pathways in the stromal cells, and the cytokines that are secreted by the immune cells, have a definitive role in orchestrating the chemoresistant property of the tumor. In this review, we systematically focus on the role played by the different microenvironmental components in determining chemoresistance of pancreatic tumors.

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Pancreatic cancer stem cells: New insight into a stubborn disease

Cited by 68 publications

References 108 publications

Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells

Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells

Prevention of pancreatic cancer in a hamster model by cAMP decrease

Microenvironment in determining chemo-resistance in pancreatic cancer: Neighborhood matters

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