Abstract
BackgroundLiver 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.MethodsHT29 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.ResultsCD44 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.ConclusionsTaken 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.
Highlights
Colorectal cancer (CRC) is the second leading cause of cancerrelated deaths in the United States [1]
In vivo selection methods, using primary cancer cell lines and comparison between pure clonal populations of isolated liver-tropic metastatic cells is a useful scientific approach for the identification of biological mechanisms enhanced during CRC liver metastasis
Our study demonstrated that the cells created through in vivo selection cycle yielded extensive liver metastasis and that aggressive behavior of these cells is associated with alterations in CD44 expression, c-MET activity and increased ability of CRC cells to adhere to endothelial cells
Summary
Colorectal cancer (CRC) is the second leading cause of cancerrelated deaths in the United States [1]. Even with comprehensive research into the biology of cancer progression, the molecular mechanisms involved in the metastatic cascade are not well characterized. The mechanisms of metastasis involve a selective and sequential series of steps, including separation from the primary tumor, invasion through surrounding tissues, entry into the circulatory system, and the establishment and proliferation in a distant location [2]. CD44, a transmembrane glycoprotein that belongs to a family of cell adhesion molecules, is involved with the progression and metastasis of multiple types of cancer [3,4,5,6] and has been associated with a poor prognosis in CRC patients [3]. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
