Concise Review: Stem Cells in Pancreatic Cancer: From Concept to Translation

Raj, Deepak; Aicher, Alexandra; Heeschen, Christopher

doi:10.1002/stem.2114

Cited by 36 publications

(24 citation statements)

References 110 publications

(143 reference statements)

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“…5c). Analysis of established marker combinations 21 for human pancreatic cancer stem cells displayed no significant differences for CD24/CD44 and CD133. Epcam, another marker was not applicable, since it is a direct target of Zeb1 repression 22 and thus strongly upregulated in KPCZ cells ( Supplementary Fig.…”

Section: Zeb1 Depletion Reduces Stemness Tumourigenic and Colonisatimentioning

confidence: 93%

The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer

et al. 2017

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Metastasis is the major cause of cancer-associated death. Partial activation of the epithelial-to-mesenchymal transition program (partial EMT) was considered a major driver of tumour progression from initiation to metastasis. However, the role of EMT in promoting metastasis has recently been challenged, in particular concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in pancreatic cancer. In contrast, we show here that in the same pancreatic cancer model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model), the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion and notably metastasis. Depletion of Zeb1 suppresses stemness, colonization capacity and in particular phenotypic/metabolic plasticity of tumour cells, probably causing the observed in vivo effects. Accordingly, we conclude that different EMT-TFs have complementary subfunctions in driving pancreatic tumour metastasis. Therapeutic strategies should consider these potential specificities of EMT-TFs to target these factors simultaneously.

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Section: Zeb1 Depletion Reduces Stemness Tumourigenic and Colonisatimentioning

confidence: 93%

The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer

et al. 2017

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“…However, many pancreatic cancer stem cells may express only one or two known surface markers, which may complicate the development of therapeutic strategies [125,126]. Some possibilities for targeting pancreatic cancer stem cells include disrupting signaling pathways that are active in cancer stem cells, such as Sonic hedgehog, Notch and mTOR, or using immunotherapy [127]. Eliminating pancreatic cancer stem cells may ultimately improve the poor prognosis of pancreatic cancer.…”

Section: • Stem Cell Therapymentioning

confidence: 99%

Pancreatic Cancer: Yesterday, Today and Tomorrow

et al. 2016

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Pancreatic cancer is one of our most lethal malignancies. Despite substantial improvements in the survival rates for other major cancer forms, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Pancreatic cancer is usually detected at an advanced stage and most treatment regimens are ineffective, contributing to the poor overall prognosis. Herein, we review the current understanding of pancreatic cancer, focusing on central aspects of disease management from radiology, surgery and pathology to oncology. Historical remarks & present stateThe first known description of pancreatic cancer is attributed to Giovanni Battista Morgagni in his 1761 publication 'de Sedibus Et Causis Morborum Per Anatomen Indagatis Libri Quinque' [1]. However, the lack of a microscopic evaluation makes the true diagnosis of ductal adenocarcinoma uncertain. The next important advancement in our understanding of pancreatic cancer did not come until 1858, when Jacob Mendez Da Costa revisited Morgagni's original work and also described the first microscopic diagnosis of adenocarcinoma, manifesting pancreatic cancer as a true disease entity [2].The history of pancreatic surgery is fairly recent and involves a combination of brave surgical pioneers, the development of surgical anesthesia and modern aseptic techniques. Some landmarks in the history of pancreatic surgery deserve to be mentioned. The first reported attempt at a pancreaticoduodenectomy was performed in 1898 by the Italian surgeon Alessandro Codivilla for a tumor involving the head of the pancreas [3]; however, the patient did not survive the postoperative period. In the same year, William Stewart Halsted from Johns Hopkins Hospital performed the first successful resection for ampullary cancer by excising portions of the duodenum and the pancreas [4]. The first successful pancreaticoduodenectomy is credited to the German surgeon Walther Carl Eduard Kausch, as part of a two-stage procedure [5]. In 1914, Georg Hirschel performed the first successful pancreaticoduodenectomy in one stage [6] and then in 1935, Allen Oldfather Whipple presented the results of a two-stage procedure involving the resection of the head of the pancreas and duodenum for ampullary carcinoma at the annual meeting of the American Surgical Association, which renewed interest in pancreatic surgery [7]. During his career, Whipple performed 37 pancreaticoduodenectomies, with the procedure evolving into a one-stage technique [8,9], and 1964-1968 1969-1973 1974-1978 1979-1983 1984-1988 1989-1993 1994-1998 1999-2003 2004-2008 2009-2013 Period of diagnosis Whipple is generally credited with popularizing the operation that still bears his name. In 1937, Alexander Brunschwig performed the first successful pancreaticoduodenectomy for pancreatic adenocarcinoma [10]. Today, with the concentration of experience in high-volume hospitals, pancreatic surgery has become a safe procedure associated with an operative mortality below 3% [11][12][13]. While major advances have been made ...

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“…CSCs are responsible for the genesis, growth, recurrence, and drug resistance of several tumours. This subpopulation of cells expresses distinct surface markers (CD133, CD44 and CD24) and proteins (Oct-4, Sox-2 and c-myc) and is thought to be involved in tumour origin, metastasis, recurrence and resistance to chemo-/radio-therapy313233. CD133 is considered to be a CSC marker in various solid tumours including the pancreas.…”

Section: Discussionmentioning

confidence: 99%

Aptamer-PEG-modified Fe3O4@Mn as a novel T1- and T2- dual-model MRI contrast agent targeting hypoxia-induced cancer stem cells

Zhu

Zhang

Liu

et al. 2016

Sci Rep

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Hypoxia-induced cancer stem cells have been known to be involved in tumour metastasis, resistance to chemo/radio therapy and tumour recurrence. Magnetic Resonance Imaging is a widely used imaging tool for cancers in clinics and research. To develop T1-positive and T2-negative dual mode MRI agents for more comprehensive and accurate diagnostic information under hypoxic conditions, a hypoxia-inducible factor-1α based aptamer and Mn(II)-modified nanoparticles D-Fe3O4@PMn were synthesized and characterized. In vitro and in vivo studies show that D-Fe3O4@PMn NPs are biocompatible and less cytotoxic and can produce significant contrast enhancement in T1- and T2-weighted MR imaging. Furthermore, the D-Fe3O4@PMn NPs enable targeted dual-contrast T1- and T2-weighted MR imaging of cancer cells expressing high levels of HIF-1α and cancer stem cell-related proteins under hypoxic condition. In conclusion, NPs with HIF-1α and Mn(II) are promising diagnostic agents for dual-mode T1 and T2 imaging by targeting cancer stem cells as they are non-toxic and biocompatible.

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Concise Review: Stem Cells in Pancreatic Cancer: From Concept to Translation

Cited by 36 publications

References 110 publications

The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer

The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer

Pancreatic Cancer: Yesterday, Today and Tomorrow

Aptamer-PEG-modified Fe3O4@Mn as a novel T1- and T2- dual-model MRI contrast agent targeting hypoxia-induced cancer stem cells

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