Multiple lineages of human breast cancer stem/progenitor cells identified by profiling with stem cell markers.
Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vitro soft agar colony formation assay and the ability to form tumors in NOD/SCID mice. We found that the expression of stem cell markers varied greatly among breast cancer cell lines. In MDA-MB-231 cells, PROCR and ESA, instead of the widely used breast cancer stem cell markers CD44(+)/CD24(-/low) and ALDH, could be used to highly enrich cancer stem/progenitor cell populations which exhibited the ability to self renew and divide asymmetrically. Furthermore, the PROCR(+)/ESA(+) cells expressed epithelial-mesenchymal transition markers. PROCR could also be used to enrich cells with colony forming ability from MB-361 cells. Moreover, consistent with the marker profiling using cell lines, the expression of stem cell markers differed greatly among primary tumors. There was an association between metastasis status and a high prevalence of certain markers including CD44(+)/CD24(-/low), ESA(+), CD133(+), CXCR4(+) and PROCR(+) in primary tumor cells. Taken together, these results suggest that similar to leukemia, several stem/progenitor cell-like subpopulations can exist in breast cancer.
Hwang-Verslues
Wendy W
WW
Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Kuo
Wen-Hung
WH
Chang
Po-Hao
PH
Pan
Chi-Chun
CC
Wang
Hsing-Hui
HH
Tsai
Sheng-Ta
ST
Jeng
Yung-Ming
YM
Shew
Jin-Yu
JY
Kung
John T
JT
Chen
Chung-Hsuan
CH
Lee
Eva Y-H P
EY
Chang
King-Jen
KJ
Lee
Wen-Hwa
WH
D000362:Agar; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051927:CD24 Antigen / Q000378:metabolism; D002455:Cell Division; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002469:Cell Separation; D000074283:Endothelial Protein C Receptor; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D000074283:Endothelial Protein C Receptor; D018960:Hyaluronan Receptors; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; D000362:Agar