Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways
| Autor: | Barzin Y. Nabet, Taewon Yoon, Diana J. Azzam, Jos Jonkers, Joyce M. Slingerland, Brianne Z. Wiemann, Andy J. Minn, Christina Twyman-Saint Victor, Hemant Ishwaran, Yu Qiu, Petra ter Brugge, Tony J. Wu, Mirjam C. Boelens, Bihui Xu |
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| Rok vydání: | 2014 |
| Předmět: |
Stromal cell
Paracrine Communication Notch signaling pathway Mice Nude Breast Neoplasms Biology Exosomes Exosome Radiation Tolerance Article General Biochemistry Genetics and Molecular Biology Paracrine signalling Cell Line Tumor Animals Humans Computer Simulation skin and connective tissue diseases Receptors Notch Biochemistry Genetics and Molecular Biology(all) Juxtacrine signalling Microvesicles STAT1 Transcription Factor rab GTP-Binding Proteins Drug Resistance Neoplasm Cancer cell Immunology Cancer research Female Interferons Stromal Cells Signal Transduction |
| DOI: | 10.17863/cam.18882 |
| Popis: | SummaryStromal communication with cancer cells can influence treatment response. We show that stromal and breast cancer (BrCa) cells utilize paracrine and juxtacrine signaling to drive chemotherapy and radiation resistance. Upon heterotypic interaction, exosomes are transferred from stromal to BrCa cells. RNA within exosomes, which are largely noncoding transcripts and transposable elements, stimulates the pattern recognition receptor RIG-I to activate STAT1-dependent antiviral signaling. In parallel, stromal cells also activate NOTCH3 on BrCa cells. The paracrine antiviral and juxtacrine NOTCH3 pathways converge as STAT1 facilitates transcriptional responses to NOTCH3 and expands therapy-resistant tumor-initiating cells. Primary human and/or mouse BrCa analysis support the role of antiviral/NOTCH3 pathways in NOTCH signaling and stroma-mediated resistance, which is abrogated by combination therapy with gamma secretase inhibitors. Thus, stromal cells orchestrate an intricate crosstalk with BrCa cells by utilizing exosomes to instigate antiviral signaling. This expands BrCa subpopulations adept at resisting therapy and reinitiating tumor growth. |
| Databáze: | OpenAIRE |
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