Rapid disorganization of mechanically interacting systems of mammary acini.

TitleRapid disorganization of mechanically interacting systems of mammary acini.
Publication TypeJournal Article
Year of Publication2014
AuthorsShi Q, Ghosh RP, Engelke H, Rycroft CH, Cassereau L, Sethian JA, Weaver VM, Liphardt JT
JournalProc Natl Acad Sci U S A
Volume111
Issue2
Pagination658-63
Date Published2014 Jan 14
ISSN1091-6490
KeywordsAcinar Cells, Breast Neoplasms, Cell Communication, Cell Line, Tumor, Cell Separation, Collagen, Escherichia coli, Female, Humans, Kaplan-Meier Estimate, Mammary Glands, Human, Microscopy, Atomic Force, Microscopy, Electron, Scanning, Microscopy, Fluorescence
Abstract

Cells and multicellular structures can mechanically align and concentrate fibers in their ECM environment and can sense and respond to mechanical cues by differentiating, branching, or disorganizing. Here we show that mammary acini with compromised structural integrity can interconnect by forming long collagen lines. These collagen lines then coordinate and accelerate transition to an invasive phenotype. Interacting acini begin to disorganize within 12.5 ± 4.7 h in a spatially coordinated manner, whereas acini that do not interact mechanically with other acini disorganize more slowly (in 21.8 ± 4.1 h) and to a lesser extent (P < 0.0001). When the directed mechanical connections between acini were cut with a laser, the acini reverted to a slowly disorganizing phenotype. When acini were fully mechanically isolated from other acini and also from the bulk gel by box-cuts with a side length <900 μm, transition to an invasive phenotype was blocked in 20 of 20 experiments, regardless of waiting time. Thus, pairs or groups of mammary acini can interact mechanically over long distances through the collagen matrix, and these directed mechanical interactions facilitate transition to an invasive phenotype.

DOI10.1073/pnas.1311312110
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID24379367
PubMed Central IDPMC3896145
Grant ListGM77856 / GM / NIGMS NIH HHS / United States
R01 CA057621 / CA / NCI NIH HHS / United States
R01 CA138818 / CA / NCI NIH HHS / United States
R01CA138818 / CA / NCI NIH HHS / United States
U54 CA143836 / CA / NCI NIH HHS / United States
U54CA143836 / CA / NCI NIH HHS / United States