Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-27649-x
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Funding
- National Pancreas Foundation Research Grant
- National Pancreas Foundation
- NPF Chapters
- Horvitz/Lebovitz Research Fund
- University of Minnesota Deborah E. Powell for Women's Health Interdisciplinary Seed Grant support [PCWH-2013-002]
- American Cancer Society [118198-IRG-58-001-52-IRG94]
- Mezin-Koats Colon Cancer Research Award
- Randy Shaver Cancer Research and Community Fund
- Litman Family Fund for Cancer Research
- Family and Friends of G. Huntington
- Central Society for Clinical and Translational Research Early Career Development Award
- Minnesota Masonic Charities
- Minnesota Medical Foundation/University of Minnesota Foundation
- Masonic Cancer Center and Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota
- NIH Clinical and Translational Science KL2 Scholar Award [8UL1TR000114]
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR002494, UL1TR000114] Funding Source: NIH RePORTER
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Intercellular communication plays a critical role in the ever-evolving landscape of invasive cancers. Recent studies have elucidated the potential role of tunneling nanotubes (TNTs) in this function. TNTs are long, filamentous, actin-based cell protrusions that mediate direct cell-to-cell communication between malignant cells. In this study, we investigated the formation of TNTs in response to variable concentrations of the chemotherapeutic drug doxorubicin, which is used extensively in the treatment of cancer patients. Doxorubicin stimulated an increased formation of TNTs in pancreatic cancer cells, and this occurred in a dose-dependent fashion. Furthermore, TNTs facilitated the intercellular redistribution of this drug between connected cells in both pancreatic and ovarian cancer systems in vitro. To provide supportive evidence for the relevance of TNTs in pancreatic cancer in vivo, we performed multiphoton fluorescence microscopy and imaged TNTs in tumor specimens resected from three human patients with pancreatic adenocarcinoma, and one with neuroendocrine carcinoma. In sum, TNT formation was upregulated in aggressive forms of pancreatic carcinoma, was further stimulated after chemotherapy exposure, and acted as a novel method for drug efflux. These findings implicate TNTs as a potential novel mechanism of drug resistance in chemorefractory forms of cancer.
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