Publication Date
2020
Journal or Book Title
Science Advances
Abstract
Tumors can undergo long periods of dormancy, with cancer cells entering a largely quiescent, nonproliferative state before reactivation and outgrowth. To understand the role of the extracellular matrix (ECM) in regulating tumor dormancy, we created an in vitro cell culture system with carefully controlled ECM substrates 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 capable of entering dormancy formed an organized, fibrillar fibronectin matrix via αvβ3 and α5β1 integrin adhesion, ROCK-generated tension, and TGFβ2 stimulation, and cancer cell outgrowth after dormancy required MMP-2–mediated fibronectin degradation. We propose this approach as a useful, 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.
DOI
https://doi.org/10.1126/sciadv.aaz4157
Volume
6
Issue
11
License
UMass Amherst Open Access Policy
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Funder
UMass SOAR Fund
Recommended Citation
Barney, Lauren E.; Hall, Christopher L.; Schwartz, Alyssa D.; Parks, Akia N.; Sparages, Christopher; Galarza, Sualyneth; Platt, Manu O.; Mercurio, Arthur; and Peyton, Shelly R., "Tumor cell–organized fibronectin maintenance of a dormant breast cancer population" (2020). Science Advances. 888.
https://doi.org/10.1126/sciadv.aaz4157