دورية أكاديمية
Treatment with tumor-treating fields (TTFields) suppresses intercellular tunneling nanotube formation in vitro and upregulates immuno-oncologic biomarkers in vivo in malignant mesothelioma
| العنوان: | Treatment with tumor-treating fields (TTFields) suppresses intercellular tunneling nanotube formation in vitro and upregulates immuno-oncologic biomarkers in vivo in malignant mesothelioma |
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| المؤلفون: | Sarkari, Akshat, Korenfeld, Sophie, Deniz, Karina, Ladner, Katherine, Wong, Phillip, Padmanabhan, Sanyukta, Vogel, Rachel I, Sherer, Laura A, Courtemanche, Naomi, Steer, Clifford, Wainer-Katsir, Kerem, Lou, Emil |
| المساهمون: | American Association for Cancer Research, American Cancer Society, Minnesota Ovarian Cancer Alliance, Dick and Lynnae Koats, University of Minnesota, The Litman Family Fund for Cancer Research, The Love Like Laurie Legacy, The Randy Shaver Cancer Research and Community Fund, National Institutes of Health |
| المصدر: | eLife ; volume 12 ; ISSN 2050-084X |
| بيانات النشر: | eLife Sciences Publications, Ltd |
| سنة النشر: | 2023 |
| المجموعة: | eLife (E-Journal - via CrossRef) |
| الوصف: | Disruption of intercellular communication within tumors is emerging as a novel potential strategy for cancer-directed therapy. Tumor-Treating Fields (TTFields) therapy is a treatment modality that has itself emerged over the past decade in active clinical use for patients with glioblastoma and malignant mesothelioma, based on the principle of using low-intensity alternating electric fields to disrupt microtubules in cancer cells undergoing mitosis. There is a need to identify other cellular and molecular effects of this treatment approach that could explain reported increased overall survival when TTFields are added to standard systemic agents. Tunneling nanotube (TNTs) are cell-contact-dependent filamentous-actin-based cellular protrusions that can connect two or more cells at long-range. They are upregulated in cancer, facilitating cell growth, differentiation, and in the case of invasive cancer phenotypes, a more chemoresistant phenotype. To determine whether TNTs present a potential therapeutic target for TTFields, we applied TTFields to malignant pleural mesothelioma (MPM) cells forming TNTs in vitro. TTFields at 1.0 V/cm significantly suppressed TNT formation in biphasic subtype MPM, but not sarcomatoid MPM, independent of effects on cell number. TTFields did not significantly affect function of TNTs assessed by measuring intercellular transport of mitochondrial cargo via intact TNTs. We further leveraged a spatial transcriptomic approach to characterize TTFields-induced changes to molecular profiles in vivo using an animal model of MPM. We discovered TTFields induced upregulation of immuno-oncologic biomarkers with simultaneous downregulation of pathways associated with cell hyperproliferation, invasion, and other critical regulators of oncogenic growth. Several molecular classes and pathways coincide with markers that we and others have found to be differentially expressed in cancer cell TNTs, including MPM specifically. We visualized short TNTs in the dense stromatous tumor material selected as regions ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.7554/elife.85383 |
| الإتاحة: | https://doi.org/10.7554/elife.85383Test https://cdn.elifesciences.org/articles/85383/elife-85383-v1.pdfTest https://cdn.elifesciences.org/articles/85383/elife-85383-v1.xmlTest https://elifesciences.org/articles/85383Test |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ ; http://creativecommons.org/licenses/by/4.0Test/ ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.9496D7B6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.7554/elife.85383 |
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