Reprogramming cancer cells: A novel approach for cancer therapy or a tool for disease-modeling?

Yılmazer, Açelya; Lázaro, Irene de; Taheri, Hadiseh

doi:10.1016/j.canlet.2015.06.027

Cited by 16 publications

(16 citation statements)

References 90 publications

(124 reference statements)

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“…iPSCs reprogrammed from cancer cells have the potential to illuminate molecular mechanisms underlying the pathogenesis of cancer ( Barrett et al., 2014 , Curry et al., 2015 , Ramos-Mejia et al., 2012c , Yilmazer et al., 2015 ). However, reprogramming human primary cancer cells remains challenging, and only a few reports have demonstrated successful reprogramming of malignant cells.…”

Section: Discussionmentioning

confidence: 99%

“…Reprogramming human primary cancer cells, however, remains challenging. Despite significant interest in generating iPSCs from leukemia cells ( Curry et al., 2015 , Ramos-Mejia et al., 2012c , Yilmazer et al., 2015 ), only a few reports have demonstrated successful reprogramming and, unfortunately, only seven of these studies reprogrammed human primary leukemias (the remaining studies used cell lines) ( Bedel et al., 2013 , Carette et al., 2010 , Gandre-Babbe et al., 2013 , Hu, 2014 , Kumano et al., 2012 , Yamamoto et al., 2015 , Ye et al., 2009 ) ( Table S1 ). Intriguingly, iPSCs from hematological primary cancer cells have exclusively been generated from chronic leukemias of myeloid origin, including Philadelphia + chronic myeloid leukemia (CML), primary myelofibrosis (PMF), JAK2-V617F + polycythemia vera (PV), and juvenile myelomonocytic leukemia (JMML) ( Table S1 ).…”

Section: Introductionmentioning

confidence: 99%

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Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency

et al. 2016

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SummaryInduced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL) has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes. OKSM(L)-expressing mono/polycistronic-, retroviral/lentiviral/episomal-, and Sendai virus vector-based reprogramming strategies failed to render iPSCs in vitro and in vivo. Addition of transcriptomic-epigenetic reprogramming “boosters” also failed to generate iPSCs from B cell blasts and B-ALL lines, and when iPSCs emerged they lacked leukemic fusion genes, demonstrating non-leukemic myeloid origin. Conversely, MLL-AF4-overexpressing hematopoietic stem cells/B progenitors were successfully reprogrammed, indicating that B cell origin and leukemic fusion gene were not reprogramming barriers. Global transcriptome/DNA methylome profiling suggested a developmental/differentiation refractoriness of MLL-rearranged B-ALL to reprogramming into pluripotency.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency

et al. 2016

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“…When the expression of tumor-suppressor genes were analyzed, cancer cells in general expressed lower levels of P16, P21 and P53, suggesting that they were not the main reason of inefficient cancer cell reprogramming. Not only basal expression levels of reprogramming and pluripotency factors, but also epigenetic basis of cancer, long-term culture conditions, heterogeneity of tumors and presence of cancer stem cells have been reported to be important players of cancer cell reprogramming [14]. Therefore, further studies are needed to delineate the other factors determining the fate of cancer cell reprogramming in melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming Human Melanocytes and Melanoma Cells with Yamanaka Factors

Yılmazer¹,

Taheri²

2018

HJBC

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Ö ZS omatik hücrelerden uyarılmış pluripotent kök (uPK) hücrelerin üretilmesi, hücre kaderinin sadece birkaç transkripsiyon faktörü kullanılarak değiştirilebileceğini göstermiştir. uPK hücrelerinin farklılaşma potansiyeli sayesinde, rejeneratif terapi dahil olmak üzere hastalık modelleme ve ilaç tarama gibi çok çeşitli potansiyel uygulamaları ortaya çıkmıştır. Bu çalışmada, Yamanaka faktörlerini kodlayan Sendai viral vektörleri kullanılarak insan melanositleri ve melanoma hücre dizilerinin yeniden programlanmasını amaçladık. Viral transfeksiyon sonrasında faz kontrast ve flüoresans mikroskobu görüntülemeleri ile melanosit kültürlerinde pluripotent kök hücre kolonilerinin ortaya çıktığı gözlenmiştir. Buna karşın, melanoma hücre kültürlerinde sadece hücre kümelenmeleri oluşmuş ve bunların pluripotens belirteçleri için pozitif olmadıkları belirlenmiştir. Bu da sağlıklı ve kanserli hücrelerin yeniden programlanması sırasında farklılıklar olduğunu göstermiştir. Yamanaka faktörlerinin, pluripotens belirteçleri ve tümör baskılayıcı genlerin bazal ifade seviyeleri analiz edilerek melanositlerde ve kanser hücre dizilerinde yeniden programlamanın farklı yanıtları anlaşılmaya çalışılmıştır. Kanserli hücrelerin etkin bir şekilde yeniden programlanmasına izin verecek çalışmaların yapılması, kanser biyolojisi ve tedavisi hakkındaki bilgimizi arttıracaktır.Anahtar Kelimeler uPK hücreleri, melanoma, melanositler, Yamanaka faktörleri, hücre programlama. A B S T R A C T

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“…In the present study, the reprogramming of A375 melanoma cells into irNCs was considered successful by characteristic neuron-like morphology, marker expression and the functional property of firing repetitive action potentials. In previous years, a number of associated experiments have demonstrated the promising potential of constructing novel culture systems in vitro by selecting candidate genes and unbiased genomes determining cellular fate ( 35 – 37 ). In the next decade, a variety of induced pluripotent stem cells and reprogrammed cells of human origin are likely to be reported.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming A375 cells to induced-resembled neuronal cells by structured overexpression of specific transcription genes

Zhang

Wei

Jiang

et al. 2016

Molecular Medicine Reports

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Induced-resembled neuronal cells (irNCs) are generated by reprogramming human melanoma cells through the introduction of key transcription factors, providing novel concepts in the treatment of malignant tumor cells and making it possible to supply neural cells for laboratory use. In the present study, irNCs were derived from A375 cells by inducing the 'forced' overexpression of specific genes, including achaete-scute homolog 1 (Ascl1), neuronal differentiation factor 1 (Neurod1), myelin transcription factor 1 (Myt1), brain protein 2 (Brn2, also termed POU3F2) and human brain-derived neurotrophic factor (h-BDNF). irNCs induced from A375 cells express multiple neuronal markers and fire action potentials, exhibiting properties similar to those of motor neurons. The reprogramming procedure comprised reverse transcription-polymerase chain reaction and immunofluorescence staining; furthermore, electrophysiological profiling demonstrated the characteristics of the induced-resembled neurons. The present study obtained a novel type of human irNC from human melanoma, which secreted BDNF continuously, providing a model for neuron-like cells. Thus, irNCs offer promise in investigating various neural diseases by using neural-like cells derived directly from the patient of interest.

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Reprogramming cancer cells: A novel approach for cancer therapy or a tool for disease-modeling?

Cited by 16 publications

References 90 publications

Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency

Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency

Reprogramming Human Melanocytes and Melanoma Cells with Yamanaka Factors

Reprogramming A375 cells to induced-resembled neuronal cells by structured overexpression of specific transcription genes

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