Department of Molecular, Cell and Cancer Biology
Cancer Biology | Cell Biology | Neoplasms
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 alphavbeta3 and alpha5beta1 integrin adhesion, ROCK-generated tension, and TGFbeta2 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.
tumors, extracellular matrix (ECM), tumor dormancy, breast cancer
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Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
DOI of Published Version
Barney LE, Hall CL, Schwartz AD, Parks AN, Sparages C, Galarza S, Platt MO, Mercurio AM, Peyton SR. Tumor cell-organized fibronectin maintenance of a dormant breast cancer population. Sci Adv. 2020 Mar 11;6(11):eaaz4157. doi: 10.1126/sciadv.aaz4157. PMID: 32195352; PMCID: PMC7065904. Link to article on publisher's site
Barney LE, Hall CL, Schwartz AD, Parks AN, Sparages C, Galarza S, Platt MO, Mercurio AM, Peyton SR. (2020). Tumor cell-organized fibronectin maintenance of a dormant breast cancer population. Open Access Publications by UMMS Authors. https://doi.org/10.1126/sciadv.aaz4157. Retrieved from https://escholarship.umassmed.edu/oapubs/4199
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