Format

Send to

Choose Destination
PLoS One. 2009 Jul 23;4(7):e6361. doi: 10.1371/journal.pone.0006361.

Differential matrix rigidity response in breast cancer cell lines correlates with the tissue tropism.

Author information

1
Department of Biological Sciences, Columbia University, New York, New York, USA.

Abstract

Metastasis to a variety of distant organs, such as lung, brain, bone, and liver, is a leading cause of mortality in the breast cancer patients. The tissue tropism of breast cancer metastasis has been recognized and studied extensively, but the cellular processes underlying this phenomenon, remain elusive. Modern technologies have enabled the discovery of a number of the genetic factors determining tissue tropism of malignant cells. However, the effect of these genetic differences on the cell motility and invasiveness is poorly understood. Here, we report that cellular responses to the mechanical rigidity of the extracellular matrix correlate with the rigidity of the target tissue. We tested a series of single cell populations isolated from MDA-MB-231 breast cancer cell line in a variety of assays where the extracellular matrix rigidity was varied to mimic the environment that these cells might encounter in vivo. There was increased proliferation and migration through the matrices of rigidities corresponding to the native rigidities of the organs where metastasis was observed. We were able to abolish the differential matrix rigidity response by knocking down Fyn kinase, which was previously identified as a critical component of the FN rigidity response pathway in healthy cells. This result suggests possible molecular mechanisms of the rigidity response in the malignant cells, indicating potential candidates for therapeutic interventions.

PMID:
19626122
PMCID:
PMC2709918
DOI:
10.1371/journal.pone.0006361
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center