Differential contractility regulates cancer stem cell migration

Rachel K Heussner, Hongrong Zhang, Guhan Qian, Mikayla J. Baker, Paolo P. Provenzano

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Cancer stem cells (CSCs) are known to have a high capacity for tumor initiation and the formation of metastases. We have previously shown that in collagen constructs mimetic of aligned extracellular matrix architectures observed in carcinomas, breast CSCs demonstrate enhanced directional and total motility compared with more differentiated carcinoma populations. Here, we show that CSCs maintain increased motility in diverse environments including on 2D elastic polyacrylamide gels of various stiffness, 3D randomly oriented collagen matrices, and ectopic cerebral slices representative of a common metastatic site. A consistent twofold increase of CSC motility across platforms suggests a general shift in cell migration mechanics between well-differentiated carcinoma cells and their stem-like counterparts. To further elucidate the source of differences in migration, we demonstrate that CSCs are less contractile than the whole population (WP) and develop fewer and smaller focal adhesions and show that enhanced CSC migration can be tuned via contractile forces. The WP can be shifted to a CSC-like migratory phenotype using partial myosin II inhibition. Inversely, CSCs can be shifted to a less migratory WP-like phenotype using microtubule-destabilizing drugs that increase contractility or by directly enhancing contractile forces. This work begins to reveal the mechanistic differences driving CSC migration and raises important implications regarding the potentially disparate effects of microtubule-targeting agents on the motility of different cell populations.

Original languageEnglish (US)
Pages (from-to)1198-1210
Number of pages13
JournalBiophysical journal
Volume122
Issue number7
DOIs
StatePublished - Apr 4 2023

Bibliographical note

Funding Information:
P.P.P. and this work was supported by Research Scholar Grant RSG-14-171-01-CSM from the American Cancer Society and the NIH ( R01CA181385 , U54CA210190 University of Minnesota Physical Sciences in Oncology Center Project 2, U54CA268069 CCBIR Center for Multiparametric Imaging of Tumor Immune Microenvironments, and R01CA245550 to P.P.P.). R.K.H. was supported by an NSF Graduate Research Fellowship 00039202 . The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of funding agencies. We thank members of the Provenzano, Ogle, Odde, Wood, and Alford labs for technical assistance and helpful conversations throughout the course of this work. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies.

Publisher Copyright:
© 2023 Biophysical Society

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
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