CD44 is of functional importance for colorectal cancer stem cells.
OBJECTIVE
Both CD44 and CD133 were reported as putative markers for isolating colorectal cancer stem cells (CSC). It remains to be resolved if both of these markers are of functional importance for colorectal CSC.


METHODS
The expression of CD44 and CD133 in normal colonic tissues and primary colorectal cancer was assessed by immunohistochemistry in a series of 60 patients on tissue microarray sections. Both in vitro clonogenic and in vivo tumorigenic assay were applied to measure CSC activities from the cells isolated from patients. Lentiviral RNA interference was used to stably knock down CD44 or CD133 in colorectal cancer cells from patients.


RESULTS
We found that CD44(+) cells displayed clustered growth and they did not colocalize with CD133(+) cells within colorectal cancer. As few as 100 CD44(+) cells from a patients' tumor initiated a xenograft tumor in vivo. A single CD44(+) cell from a tumor could form a sphere in vitro which has characteristic stem cell properties and was able to generate a xenograft tumor resembling the properties of the primary tumor. Knockdown of CD44, but not CD133, strongly prevented clonal formation and inhibited tumorigenicity in xenograft model.


CONCLUSIONS
These results indicate that CD44 is a robust marker and is of functional importance for colorectal CSC for cancer initiation.
Du
Lei
L
Joint Laboratory of Apoptosis and Cancer Biology, the State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Wang
Hongyi
H
He
Leya
L
Zhang
Jingyu
J
Ni
Biyun
B
Wang
Xiaohui
X
Jin
Haijing
H
Cahuzac
Nathalie
N
Mehrpour
Maryam
M
Lu
Youyong
Y
Chen
Quan
Q
D000071916:AC133 Antigen; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010455:Peptides / Q000032:analysis*; D034622:RNA Interference
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse