Cellular Reprogramming Using Defined Factors and MicroRNAs

Eguchi, Takanori; Kuboki, Takuo

doi:10.1155/2016/7530942

Cited by 26 publications

(20 citation statements)

References 101 publications

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“…Stem cells were first found in hematopoietic cells and thus designated hematopoietic stem cells (HSCs) [ 45 ]. Unequivocal proof of HSCs has given way to the prospective isolation of tissue-specific stem and progenitor cells [ 34 , 35 , 46 ]. Tumors may often originate from the transformation of normal stem cells, and cancer cells may include sub-populations of CSCs [ 28 , 30 , 45 ].…”

Section: Introductionmentioning

confidence: 99%

Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment

et al. 2018

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Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets. Seven GLA-forming cell lines were derived from adenocarcinoma among the 8 lines. A neuroendocrine adenocarcinoma cell line PC-3 formed asymmetric GLA with ductal structures on the NCPs and rapidly growing asymmetric tumors that metastasized to lymph nodes in immunocompromised mice. In contrast, another adenocarcinoma cell line DU-145 formed spheroids in vitro and spheroid-like tumors in vivo that did not metastasize to lymph nodes until day 50 after transplantation. Culture in the 3D nanoenvironment and in a defined stem cell medium enabled the neuroendocrine adenocarcinoma cells to form slowly growing large organoids that expressed multiple stem cell markers, neuroendocrine markers, intercellular adhesion molecules, and oncogenes in vitro. In contrast, the more commonly used 2D serum-contained environment reduced intercellular adhesion and induced mesenchymal transition and promoted rapid growth of the cells. In addition, the 3D stemness nanoenvironment promoted secretion of HSP90 and EpCAM-exosomes, a marker of CSC phenotype, from the neuroendocrine organoids. These findings indicate that the NCP-based 3D environment enables cells to form stem cell tumoroids with multipotency and model more accurately the in vivo tumor status at the levels of morphology and gene expression.

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Section: Introductionmentioning

confidence: 99%

Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment

et al. 2018

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“…We have shown that cancer cell aggregation led to formation of hypoxic tumoroids with robust secretion of EpCAM-exosomes and marked upregulation of reprogramming and stemness genes as increased CIC/CSC traits ( 2 ). A term of cellular “reprogramming” has been major after the development of induced pluripotent stem (iPS) cells ( 35 – 37 ) and more recently used in cancer studies as well ( 38 – 42 ). Intra-tumoral hypoxia, as well as a hypoxic milieu, can increase CIC/CSC properties through the hypoxia-inducible factor 1α (HIF-1α)-mediated induction of CIC/CSC genes, oncogenes, and ABC transporter genes ( 2 , 43 – 45 ).…”

Section: Introductionmentioning

confidence: 99%

Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells

et al. 2018

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The ATP-binding cassette transporter G1 (ABCG1) is a cholesterol lipid efflux pump whose role in tumor growth has been largely unknown. Our transcriptomics revealed that ABCG1 was powerfully expressed in rapidly metastatic, aggregative colon cancer cells, in all the ABC transporter family members. Coincidently, genetic amplification of ABCG1 is found in 10–35% of clinical samples of metastatic cancer cases. Expression of ABCG1 was further elevated in three-dimensional tumoroids (tumor organoids) within stemness-enhancing tumor milieu, whereas depletion of ABCG1 lowered cellular aggregation and tumoroid growth in vitro as well as hypoxia-inducible factor 1α in cancer cells around the central necrotic areas in tumors in vivo. Notably, depletion of ABCG1 triggered the intracellular accumulation of extracellular vesicles (EVs) and regression of tumoroids. Collectively, these data suggest that ABCG1 plays a crucial role in tumorigenesis in metastatic cancer and that depletion of ABCG1 triggers tumor regression with the accumulation of EVs and their derivatives and cargos, implicating a novel ABCG1-targeting therapeutic strategy by which redundant and toxic substances may be accumulated in tumors leading to their regression.

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“…MiRNAs are highly conserved ncRNAs that exert versatile biological functions. 28,29 Zhu et al indicated that LncRNA-ATB could promote viability, migration, and angiogenesis in human microvascular endothelial cells by sponging microRNA-195. 30 In addition, lncRNA-ATB could promote the progression of colorectal cancer by regulating miR-200c/CDK2 axis.…”

Section: Discussionmentioning

confidence: 99%

<p>LncRNA-ATB Promotes the Tumorigenesis of Ovarian Cancer via Targeting miR-204-3p</p>

Yuan

Hua

Guo

et al. 2020

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Background: Ovarian cancer ranks fifth among the most prevalent cancer type in females all over the world. It is the second most frequent malignant tumor which accounts for 3% of cancer in females. Therefore, to explore the mechanism of carcinogenesis in ovarian cancer is important to develop new treatment methods. It has been previously found that lncRNA-ATB could promote the tumorigenesis of malignant tumors. However, the role of lncRNA-ATB during the progression of ovarian cancer remains unclear. Methods: Gene expressions in tissues or cells were detected by using qRT-PCR. Western blot was performed to investigate the protein expressions in ovarian cancer cells. Cell apoptosis was tested by flow cytometry. Moreover, the correction between lncRNA-ATB and miR-204-3p was examined by Dual-luciferase reporter assay and RNA pulldown. Cell proliferation and invasion were detected by CCK-8, Ki-67 staining and transwell assay, respectively. Finally, xenograft mice model was established to confirm the result of in vitro experiments. Results: LncRNA-ATB silencing significantly inhibited the proliferation and induced apoptosis of ovarian cancer cells. In addition, luciferase activity suggested that lncRNA-ATB negatively regulated miR-204-3p in ovarian cancer. Besides, Nidogen 1 (NID1) was the direct target of miR-204-3p. Overexpression of NID1 could notably reverse the inhibitory effect of lncRNA-ATB knockdown on the progression of ovarian cancer. Finally, lncRNA-ATB silencing notably attenuated the severity of ovarian cancer in vivo. Conclusion: Downregulation of lncRNA-ATB significantly inhibited the tumorigenesis of ovarian cancer in vitro and in vivo, which may serve as a potential novel target for the treatment of ovarian cancer.

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Cellular Reprogramming Using Defined Factors and MicroRNAs

Cited by 26 publications

References 101 publications

Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment

Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment

Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells

<p>LncRNA-ATB Promotes the Tumorigenesis of Ovarian Cancer via Targeting miR-204-3p</p>

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