The Ever-Evolving Concept of the Cancer Stem Cell in Pancreatic Cancer

Valle, Sandra; Martín-Hijano, Laura; Alcalá, Sonia; Alonso-Nocelo, Marta; Sáinz, Bruno

doi:10.3390/cancers10020033

Cited by 93 publications

(90 citation statements)

References 169 publications

(200 reference statements)

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“…ª 2018 The Authors EMBO Molecular Medicine 10: e9085 | 2018 stem cell-like phenotype associated with pancreatic cancer (Valle et al, 2018), although this proposition needs experimental evidence.…”

Section: Discussionmentioning

confidence: 99%

Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program

et al. 2018

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Epithelial‐to‐mesenchymal transition (EMT) is a recognized eukaryotic cell differentiation program that is also observed in association with invasive tumors. Partial EMT program in carcinomas imparts cancer cells with mesenchymal‐like features and is proposed as essential for metastasis. Precise determination of the frequency of partial EMT program in cancer cells in tumors and its functional role in metastases needs unraveling. Here, we employed mesenchymal cell reporter mice driven by αSMA‐Cre and Fsp1‐Cre with genetically engineered mice that develop spontaneous pancreatic ductal adenocarcinoma (PDAC) to monitor partial EMT program. Both αSMA‐ and Fsp1‐Cre‐mediated partial EMT programs were observed in the primary tumors. The established metastases were primarily composed of cancer cells without evidence for a partial EMT program, as assessed by our fate mapping approach. In contrast, metastatic cancer cells exhibiting a partial EMT program were restricted to isolated single cancer cells or micrometastases (3–5 cancer cells). Collectively, our studies identify large metastatic nodules with preserved epithelial phenotype and potentially unravel a novel metastasis program in PDAC.

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Section: Discussionmentioning

confidence: 99%

Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program

et al. 2018

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“…CSCs possess variable histological characteristics which makes them prone to chemoresistance. Conventional chemotherapeutic agents target and attack the bulk population of cancer cells in a tumor, leaving CSCs unaffected and fully capable of giving rise to the relapsed tumor . This attributes to CSCs being the ideal candidates for developing targeted chemotherapies with recent advances in the assay development .…”

Section: Discussionmentioning

confidence: 99%

“…29 Consistent with the finding observed for the in vitro studies, there was a significant decrease in the expression of each of the transcription factors (in terms of positively stained cells) examined in the samples from BMJ-treated mice compared to controls (Figure 8). Quantitative analyses showed a decrease in SOX2 expression by ∼80% ( Figure 8A) and that of OCT4, NANOG, and PDX1 by ∼67% decrease in the samples from BMJ-fed mice compared to controls expression ( Figure 8B 30 This attributes to CSCs being the ideal candidates for developing targeted chemotherapies with recent advances in the assay development. 31 PanC-CSCs were first established in 2007, and since then techniques have been developed to identify them as potential biomarkers of PanC.…”

Section: Bmj Downregulates the Expression Of Csc Associated Transcrmentioning

confidence: 93%

Bitter melon juice exerts its efficacy against pancreatic cancer via targeting both bulk and cancer stem cells

Dhar

Deep

Kumar

et al. 2018

Molecular Carcinogenesis

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Pancreatic cancer (PanC) is one of the deadliest malignancies worldwide and frontline treatment with gemcitabine becomes eventually ineffective due to increasing PanC resistance, suggesting additional approaches are needed to manage PanC. Recently, we have shown the efficacy of bitter melon juice (BMJ) against PanC cells, including those resistant to gemcitabine. Since cancer stem cells (CSCs) are actively involved in PanC initiation, progression, relapse and drug-resistance, here we assessed BMJ ability in targeting pancreatic cancer-associated cancer stem cells (PanC-CSCs). We found BMJ efficacy against CD44+/CD24+/EpCAMhigh enriched PanC-CSCs in spheroid assays; BMJ also increased the sensitivity of gemcitabine-resistant PanC-CSCs. Exogenous addition of BMJ to PanC-CSC generated spheroids (not pre-exposed to BMJ) also significantly reduced spheroid number and size. Mechanistically, BMJ effects were associated with a decrease in the expression of genes and proteins involved in PanC-CSC renewal and proliferation. Specifically, immunofluorescence staining showed that BMJ decreases protein expression/nuclear localization of CSC-associated transcription factors SOX2, OCT4 and NANOG, and CSC marker CD44. Immunohistochemical analysis of MiaPaCa2 xenografts from BMJ treated animals also showed a significant decrease in the levels of CSC-associated transcription factors. Together, these results show BMJ potential in targeting PanC-CSC pool and associated regulatory pathways, suggesting the need for further investigation of its efficacy against PanC growth and progression including gemcitabine-resistant PanC.

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“…Recent studies have revealed that autophagy is crucial for cancer stem cell growth and can enrich breast cancer cell proliferation . Studies have also revealed a positive correlation between pancreatic cancer stem cell markers (ALDH, CD44, CD133) and autophagy factors . Moreover, autophagy is essential for maintaining the self‐renewal capacity of cancer stem cells.…”

Section: Resultsmentioning

confidence: 99%

Detecting the Origin of Cancer‐Mobile Quantum Probe for Single Cancer Stem Cell Detection

Ganesh

Venkatakrishnan

Tan

2019

Adv Funct Materials

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Cancer stem cells (CSC) are believed to be the driving force of cancer metastases and are a rare population of self‐renewing cells that contribute majorly to the poor outcomes of cancer therapy. The detection of CSC is of utmost importance to shed light on the indestructible nature of certain solid tumors and their metastatic ability. However, tumors tend to harbor CSCs in a specialized niche, making the detection process difficult. Currently, there is no method available to detect CSCs. The significance of this work is twofold. First, to the best of the knowledge, it is the first time that the detection of CSC is demonstrated. This approach simultaneously detects both the phenotypic and the metabolic state of the cell, thus enabling universal detection of CSC with high accuracy. Second, to the best of the knowledge, for the first time, light is shed on cell chemistry of CSC in their dedicated niche to facilitate a better understanding of the key players involved in the metabolic rewiring of CSC. This work will enable a better understanding of the fundamentals of CSCs, which are critical for the early diagnosis of cancer and the development of therapies for the cure of cancer.

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The Ever-Evolving Concept of the Cancer Stem Cell in Pancreatic Cancer

Cited by 93 publications

References 169 publications

Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program

Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program

Bitter melon juice exerts its efficacy against pancreatic cancer via targeting both bulk and cancer stem cells

Detecting the Origin of Cancer‐Mobile Quantum Probe for Single Cancer Stem Cell Detection

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