Cell cycle (Georgetown, Tex.), 2016-06, Vol.15 (12), p.1531-1537
2016
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Details
- Autor(en) / Beteiligte
- Titel
- Human colonic fibroblasts regulate stemness and chemotherapy resistance of colon cancer stem cells
- Ist Teil von
- Cell cycle (Georgetown, Tex.), 2016-06, Vol.15 (12), p.1531-1537
- Ort / Verlag
- United States: Taylor & Francis
- Erscheinungsjahr
- 2016
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- There is increasing evidence that cancers are heterogeneous and contain a hierarchical organization consisting of cancer stem cells and their differentiated cell progeny. These cancer stem cells are at the core of the tumor as they represent the clonogenic cells within a tumor. Moreover, these cells are considered to contain selective therapy resistance, which suggests a pivotal role in therapy resistance and tumor relapse. Here we show that differentiated cells can re-acquire stemness through factors secreted from fibroblasts. This induced CSC state also coincides with re-acquisition of resistance to chemotherapy. Resistance induced in newly formed CSCs is mediated by the anti-apoptotic molecule BCLXL and inhibition of BCLXL with the BH3 mimetic ABT-737 sensitizes these cancer cells toward chemotherapy. These data point to an important interplay between tumor cells and their microenvironment in the regulation of stemness and therapy resistance.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1538-4101eISSN: 1551-4005DOI: 10.4161/15384101.2014.973321Titel-ID: cdi_proquest_miscellaneous_1799559925
- Format
- –
- Schlagworte
- ABT-737, AC133 Antigen - genetics, AC133 Antigen - metabolism, Antineoplastic Agents - pharmacology, apoptosis, bcl-X Protein - genetics, bcl-X Protein - metabolism, BCLXL, Biological Factors - pharmacology, Biological Factors - secretion, Biomarkers - metabolism, Biphenyl Compounds - pharmacology, cancer stem cell, Cell Communication, Cell Death, Cell Differentiation, chemotherapy, Colonic Neoplasms - genetics, Colonic Neoplasms - metabolism, Colonic Neoplasms - pathology, colorectal cancer, Culture Media, Conditioned - chemistry, Culture Media, Conditioned - pharmacology, Drug Resistance, Neoplasm, Extra View, fibroblast, Fibroblasts - drug effects, Fibroblasts - pathology, Fibroblasts - secretion, Gene Expression Regulation, Neoplastic, Genes, Reporter, Green Fluorescent Proteins - genetics, Green Fluorescent Proteins - metabolism, Humans, Keratin-20 - genetics, Keratin-20 - metabolism, microenvironment, Mucin-2 - genetics, Mucin-2 - metabolism, Neoplastic Stem Cells - drug effects, Neoplastic Stem Cells - metabolism, Neoplastic Stem Cells - pathology, Nitrophenols - pharmacology, Piperazines - pharmacology, Primary Cell Culture, Receptors, G-Protein-Coupled - genetics, Receptors, G-Protein-Coupled - metabolism, resistance, Signal Transduction, Spheroids, Cellular - drug effects, Spheroids, Cellular - metabolism, Spheroids, Cellular - pathology, Sulfonamides - pharmacology