CD133 expression is not selective for tumor-initiating or radioresistant cell populations in the CRC cell lines HCT-116.
OBJECTIVE
CD133 is controversially discussed as putative (surrogate) marker for cancer stem/tumor-initiating cell populations (CSC/TIC) in epithelial tumors including colorectal carcinomas (CRCs). We studied CD133 expression in established CRC cell lines and examined in vitro behavior, radioresponse and in vivo tumor formation of CD133(+/-) subpopulations of one cell line of interest.


METHODS
Ten CRC cell lines were analyzed for CD133 expression using flow cytometry and Western blotting. CD133+ and CD133(-) HCT-116 subpopulations were separated by FACS and studied in 2-D and 3-D culture and colony formation assays after irradiation. Subcutaneous xenograft formation was monitored in NMRI (nu/nu) mice.


CONCLUSIONS
CRC cell lines could be classified into three groups: (i) CD133(-), (ii) CD133+ and (iii) those with two distinct CD133+ and CD133(-) subpopulations. Isolated CD133(+/-) HCT-116 subpopulations were studied relative to the original fraction. No difference was found in 2-D growth, spheroid formation or radioresponse in vitro. Also, tumor formation and growth rate did not differ for the sorted subpopulations. However, a subset of xenografts originated from CD133(-) HCT-116 showed a striking enrichment in the CD133+ fraction. Our data show that CD133 expression is not selective for sphere forming, tumor-initiating or radioresistant subpopulations in the HCT-116 CRC cell lines. This implies that CD133 cannot be regarded as a CSC/TIC marker in all CRC cell lines and that functional measurements of tumor formation have to generally accompany CSC/TIC-directed mechanistic or therapeutic studies.
Dittfeld
Claudia
C
Tumor Pathophysiology, OncoRay-Center for Radiation Research in Oncology, Dresden University of Technology, Germany.
Dietrich
Antje
A
Peickert
Susann
S
Hering
Sandra
S
Baumann
Michael
M
Grade
Marian
M
Ried
Thomas
T
Kunz-Schughart
Leoni A
LA
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor / Q000378:metabolism / Q000528:radiation effects*; D002469:Cell Separation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000378:metabolism*; D045325:HCT116 Cells / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells; D010455:Peptides / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics*; D012680:Sensitivity and Specificity
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse