Abstract
Background
Liver metastasis is the most common cause of death in patients with colorectal cancer. Despite extensive research into the biology of cancer progression, the molecular mechanisms that drive colorectal cancer metastasis are not well characterized.
Methods
HT29 LM1, HT29 LM2, HT29 LM3 cell lines were derived from the human colorectal cancer cell line HT29 following multiple rounds of in vivo selection in immunodeficient mice.
Results
CD44 expression, a transmembrane glycoprotein involved in cell-cell and cell-matrix adhesions, and cancer cells adhesion to endothelial cells was increased in all in vivo selected cell lines, with maximum CD44 expression and cancer cells adhesion to endothelial cells in the highly metastatic HT29 LM3 cell line. Activation of c-Met upon hepatocyte growth factor (HGF) stimulation in the in vivo selected cell lines is CD44 independent. In vitro separation of CD44 high and low expression cells from HT29 LM3 cell line with FACS sorting confirmed that c-Met activation is CD44 independent upon hepatocyte growth factor stimulation. Furthermore, in vivo evaluation of CD44 low and high expressing HT29 LM3 cells demonstrated no difference in liver metastasis penetrance.
Conclusions
Taken together, our findings indicate that the aggressive metastatic phenotype of in vivo selected cell lines is associated with overexpression of CD44 and activation of c-MET. We demonstrate that c-Met activation is CD44 independent upon hepatocyte growth factor stimulation and confirm that CD44 expression in HT29 LM3 cell line is not responsible for the increase in metastatic penetrance in HT29 LM3 cell line.
Document Type
Article
Publication Date
5-13-2014
Digital Object Identifier (DOI)
http://dx.doi.org/10.1371/journal.pone.0097432
Repository Citation
Elliott, Victoria Allison; Rychahou, Piotr G.; Zaytseva, Yekaterina Y.; and Evers, B. Mark, "Activation of c-Met and Upregulation of CD44 Expression are Associated with the Metastatic Phenotype in the Colorectal Cancer Liver Metastasis Model" (2014). Markey Cancer Center Faculty Publications. 16.
https://uknowledge.uky.edu/markey_facpub/16
Notes/Citation Information
Published in PLOS One, v. 9, issue. 5, e97432.
© 2014 Elliott et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.