Article

Reprogramming of gastrointestinal cancer cells

Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan.
Cancer Science (Impact Factor: 3.52). 12/2011; 103(3):393-9. DOI: 10.1111/j.1349-7006.2011.02184.x
Source: PubMed

ABSTRACT

Cell reprogramming reverts cells to multipotent, preprogrammed states by re-establishing epigenetic markers. It can also induce considerable malignant phenotype modification. Because key events in cancer relapse and metastasis, including epithelial-mesenchymal transition phenotypes, are regulated primarily by reversible and transient epigenetic modifications rather than the accumulation of irreversible and stable genetic abnormalities, studying dynamic mechanisms regulating these biological processes is important. Transcription factors for induced pluripotent stem cells and non-coding microRNAs allow pluripotent phenotype induction. We present the current knowledge of the possible applications of cell reprogramming in reducing aggressive phenotype expression, which can induce tumor cell hibernation and maintain appropriate phenotypes, thereby minimizing relapse and metastasis after surgical resection of gastrointestinal cancer.

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Available from: Taroh Satoh, Dec 10, 2014
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    • "Although its relatively low reprogramming efficiency may still be a disadvantage, significant improvement can be achieved following multiple repeated transfections (Okita et al., 2008;Okita et al., 2010). However, despite considerable interest in the field, only a few reports to date have demonstrated successful reprogramming of malignant cells to pluripotency, all of which adopt the viral approach (lentivirus or retrovirus) (Carette et al., 2010; Dewi et al., 2012; Lin and Chui, 2012; Lin et al., 2008; Miyoshi et al., 2010; Nagai et al., 2010). Thus, the generation of cancer-derived iPSCs remains a challenge, and there are many hurdles still to be addressed. "
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    ABSTRACT: Abstract In spite of considerable interest in the field, reprogramming induced pluripotent stem cells (iPSCs) directly from cancer cells has encountered considerable challenges, including the extremely low reprogramming efficiency and instability of cancer-derived iPSCs (C-iPSCs). In this study, we aimed to identify the main obstacles that limit cancer cell reprogramming. Through a detailed multidimensional kinetic optimization, a highly optimized protocol is established for reprogramming C-iPSCs using nonviral plasmid vectors. We demonstrated how the initial cancer cell density seeded could be the most critical factor ultimately affecting C-iPSCs reprogramming. We have consistently achieved an unprecedented high C-iPSC reprogramming efficiency, establishing stable colonies with typical iPSC morphology, up to 50% of which express the iPSC phenotypic (Oct3/4, Sox2, Nanog) and enzymatic (alkaline phosphatase) markers. Furthermore, established C-iPSC lines were shown to be capable of forming teratomas in vivo, containing cell types and tissues from each of the embryonic germ layers, fully consistent with their acquisition of pluripotency. This protocol was tested and confirmed in two completely unrelated human lung adenocarcinoma (A549) and mouse melanoma (B16f10) cancer cell lines and thus offers a potentially valuable method for generating effectively virus-free C-iPSCs for future applications.
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