The stem cell marker CD133 associates with enhanced colony formation and cell motility in colorectal cancer

Elsaba, Tarek M. A., Martinez-Pomares, Luisa, Robins, Adrian R., Crook, Simon, Seth, Rashmi, Jackson, Darryl, McCart, Amy, Silver, Andrew R., Tomlinson, Ian P. M. and Ilyas, Mohammad (2010) The stem cell marker CD133 associates with enhanced colony formation and cell motility in colorectal cancer. PLoS One, 5 5: 1-11. doi:10.1371/journal.pone.0010714

Author Elsaba, Tarek M. A.
Martinez-Pomares, Luisa
Robins, Adrian R.
Crook, Simon
Seth, Rashmi
Jackson, Darryl
McCart, Amy
Silver, Andrew R.
Tomlinson, Ian P. M.
Ilyas, Mohammad
Title The stem cell marker CD133 associates with enhanced colony formation and cell motility in colorectal cancer
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2010-05-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0010714
Open Access Status DOI
Volume 5
Issue 5
Start page 1
End page 11
Total pages 11
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
Abstract CD133 is a membrane molecule that has been, controversially, reported as a CSC marker in colorectal cancer (CRC). In this study, we sought to clarify the expression and role of CD133 in CRC. Initially the size of the CD1332expressing (CD133+) population in eight well-described CRC cell lines was measured by flow cytometry and was found to range from 0% to >95%. The cell line HT29 has a CD133+ population of >95% and was chosen for functional evaluation of CD133 after gene knockdown by RNA interference. A time course assay showed that CD133 inhibition had no significant effect on cell proliferation or apoptosis. However, CD133 knockdown did result in greater susceptibility to staurosporine-induced apoptosis (p = 0.01) and reduction in cell motility (p<0.04). Since gene knockdown may cause "off-target" effects, the cell line SW480 (which has a CD133+ population of 40%) was sorted into pure CD133+ and CD1332 populations to allow functional comparison of isogenic populations separated only by CD133 expression. In concordance with the knockdown experiments, a time course assay showed no significant proliferative differences between the CD133+/CD1332 populations. Also greater resistance to staurosporine-induced apoptosis (p = 0.008), greater cell motility (p = 0.03) and greater colony forming efficiency was seen in the CD133+ population than the CD1332 population in both 2D and 3D culture (p<0.0001 and p<0.003 respectively). Finally, the plasticity of CD133 expression in tumour cells was tested. Quantitative PCR analysis showed there was transcriptional repression in the CD1332 population of SW480. Prolonged culture of a pure CD1332 population resulted in re-emergence of CD133+ cells. We conclude that CD133 expression in CRCs is associated with some features attributable to stemness and that there is plasticity of CD133 expression. Further studies are necessary to delineate the mechanistic basis of these features.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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