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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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