دورية أكاديمية
Dissecting tumor metabolic heterogeneity: Telomerase and large cell size metabolically define a sub-population of stem-like, mitochondrial-rich, cancer cells.
| العنوان: | Dissecting tumor metabolic heterogeneity: Telomerase and large cell size metabolically define a sub-population of stem-like, mitochondrial-rich, cancer cells. |
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| المؤلفون: | Lamb, Rebecca, Ozsvari, Bela, Bonuccelli, Gloria, Smith, Duncan L, Pestell, Richard, Martinez-Outshoorn, MD, Ubaldo E., Clarke, Robert B, Sotgia, Federica, Lisanti, Michael P |
| المصدر: | Kimmel Cancer Center Faculty Papers |
| بيانات النشر: | Jefferson Digital Commons |
| سنة النشر: | 2015 |
| المجموعة: | Jefferson Digital Commons (Thomas Jefferson University, Philadelphia) |
| مصطلحات موضوعية: | The Sidney Kimmel Cancer Center, Thomas Jefferson University, Article, cell culture, cell fractionation, cell heterogeneity, cell isolation, cell metabolism, cell subpopulation, controlled study, epithelial mesenchymal transition, fluorescence activated cell sorting, genetic transfection, human, human cell, immortalized cell line, major clinical study, MCF 7 cell line, mitochondrial volume, phenotype, protein expression, protein synthesis, transcription regulation, Oncology |
| الوصف: | Tumor cell metabolic heterogeneity is thought to contribute to tumor recurrence, distant metastasis and chemo-resistance in cancer patients, driving poor clinical outcome. To better understand tumor metabolic heterogeneity, here we used the MCF7 breast cancer line as a model system to metabolically fractionate a cancer cell population. First, MCF7 cells were stably transfected with an hTERT-promoter construct driving GFP expression, as a surrogate marker of telomerase transcriptional activity. To enrich for immortal stem-like cancer cells, MCF7 cells expressing the highest levels of GFP (top 5%) were then isolated by FACS analysis. Notably, hTERT-GFP(+) MCF7 cells were significantly more efficient at forming mammospheres (i.e., stem cell activity) and showed increased mitochondrial mass and mitochondrial functional activity, all relative to hTERT-GFP(-) cells. Unbiased proteomics analysis of hTERT-GFP(+) MCF7 cells directly demonstrated the over-expression of 33 key mitochondrial proteins, 17 glycolytic enzymes, 34 ribosome-related proteins and 17 EMT markers, consistent with an anabolic cancer stem-like phenotype. Interestingly, MT-CO2 (cytochrome c oxidase subunit 2; Complex IV) expression was increased by >20-fold. As MT-CO2 is encoded by mt-DNA, this finding is indicative of increased mitochondrial biogenesis in hTERT-GFP(+) MCF7 cells. Importantly, most of these candidate biomarkers were transcriptionally over-expressed in human breast cancer epithelial cells in vivo. Similar results were obtained using cell size (forward/side scatter) to fractionate MCF7 cells. Larger stem-like cells also showed increased hTERT-GFP levels, as well as increased mitochondrial mass and function. Thus, this simple and rapid approach for the enrichment of immortal anabolic stem-like cancer cells will allow us and others to develop new prognostic biomarkers and novel anti-cancer therapies, by specifically and selectively targeting this metabolic sub-population of aggressive cancer cells. Based on our proteomics and functional ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://jdc.jefferson.edu/kimmelccfp/53Test; https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1053&context=kimmelccfpTest |
| الإتاحة: | https://jdc.jefferson.edu/kimmelccfp/53Test https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1053&context=kimmelccfpTest |
| رقم الانضمام: | edsbas.F8194783 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |