University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Department of Molecular, Cell and Cancer Biology
Publication Date
2019-07-01
Document Type
Article Preprint
Disciplines
Cancer Biology
Abstract
Tumors can undergo long periods of dormancy, with cancer cells entering a largely quiescent, non-proliferative state before reactivation and outgrowth. For a patient, these post-remission tumors are often drug resistant and highly aggressive, resulting in poor prognosis. To understand the role of the extracellular matrix (ECM) in regulating tumor dormancy, we created an in vitro cell culture system that combines carefully controlled ECM substrates with nutrient deprivation to observe entrance into and exit from dormancy with live imaging. We saw that cell populations capable of surviving entrance into long-term dormancy were heterogeneous, containing quiescent, cell cycle arrested, and actively proliferating cells. Cell populations that endured extended periods of serum-deprivation-induced dormancy formed an organized, fibrillar fibronectin matrix via αvβ3 and α5β1 integrin adhesion, ROCK-generated tension, and TGFβ2 stimulation. We surmised that the fibronectin matrix was primarily a mediator of cell survival, not proliferation, during the serum-deprivation stress, bacause cancer cell outgrowth after dormancy required MMP-2-mediated fibronectin degradation. Given the difficulty of animal models in observing entrance and exit from dormancy in real-time, we propose this approach as a new, in vitro method to study factors important in regulating dormancy, and we used it here to elucidate a role for fibronectin deposition and MMP activation.
Keywords
cancer biology, tumors, fibronectin, in vitro, turmor dormancy, remission, extracellular matrix
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY 4.0 International license.
DOI of Published Version
10.1101/686527
Source
bioRxiv 686527; doi: https://doi.org/10.1101/686527. Link to preprint on bioRxiv service.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Barney LE, Hall CL, Schwartz AD, Parks AN, Sparages C, Galarza S, Platt MO, Mercurio AM, Peyton SR. (2019). Tumor cell-organized fibronectin is required to maintain a dormant breast cancer population. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/686527. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1620
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.