Tumor cell-organized fibronectin maintenance of a dormant breast cancer population.
Sci Adv
; 6(11): eaaz4157, 2020 03.
Article
in En
| MEDLINE
| ID: mdl-32195352
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 αvß3 and α5ß1 integrin adhesion, ROCK-generated tension, and TGFß2 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Fibronectins
/
Neoplasm Proteins
Limits:
Female
/
Humans
Language:
En
Journal:
Sci Adv
Year:
2020
Document type:
Article
Affiliation country:
United States