Tumor cell-organized fibronectin is required to maintain a dormant breast cancer population [preprint]
Authors
Barney, Lauren E.Hall, Christopher L.
Schwartz, Alyssa D.
Parks, Akia N.
Sparages, Christopher
Galarza, Sualyneth
Platt, Manu O.
Mercurio, Arthur M.
Peyton, Shelly R.
UMass Chan Affiliations
Department of Molecular, Cell and Cancer BiologyDocument Type
PreprintPublication Date
2019-07-01Keywords
cancer biologytumors
fibronectin
in vitro
turmor dormancy
remission
extracellular matrix
Cancer Biology
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Show full item recordAbstract
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.Source
bioRxiv 686527; doi: https://doi.org/10.1101/686527. Link to preprint on bioRxiv service.
DOI
10.1101/686527Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29390Rights
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/686527
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Except where otherwise noted, this item's license is described as 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.