1475-2867-10-24.pdf (1.34 MB)
0/0

The extracellular matrix microtopography drives critical changes in cellular motility and Rho A activity in colon cancer cells

Download (1.34 MB)
journal contribution
posted on 29.04.2011 by Rebecca Rapier, Jameela Huq, Ramana Vishnubhotla, Marinka Bulic, Cecile M. Perrault, Vitali Metlushko, Michael Cho, Roger T. S. Tay, Sarah C. Glover
We have shown that the microtopography (mT) underlying colon cancer changes as a tumor de-differentiates. We distinguish the well-differentiated mT based on the increasing number of "pits" and poorly differentiated mT on the basis of increasing number of "posts." We investigated Rho A as a mechanosensing protein using mT features derived from those observed in the ECM of colon cancer. We evaluated Rho A activity in less-tumorogenic (Caco-2 E) and more tumorigenic (SW620) colon cancer cell-lines on microfabricated pits and posts at 2.5 mu m diameter and 200 nm depth/height. In Caco-2 E cells, we observed a decrease in Rho A activity as well as in the ratio of G/F actin on surfaces with either pits or posts but despite this low activity, knockdown of Rho A led to a significant decrease in confined motility suggesting that while Rho A activity is reduced on these surfaces it still plays an important role in controlling cellular response to barriers. In SW620 cells, we observed that Rho A activity was greatest in cells plated on a post microtopography which led to increased cell motility, and an increase in actin cytoskeletal turnover.

Funding

We are grateful to the American Gastroenterological Association, the University of Illinois GILD, and the National Institutes of Health (1 RO1 CA113975-A2) for funding this work.

History

Publisher Statement

Post print version of article may differ from published version. The definitive version is available through BioMed Central at DOI: 10.1186/1475-2867-10-24

Publisher

BioMed Central

Language

en_US

issn

1475-2867

Issue date

28/07/2010

Exports

Categories

Exports