Reduction of CD44(+)/CD24(-) breast cancer cells by conventional cytotoxic chemotherapy.
Breast cancer cells with the CD44(+)/CD24(-) phenotype have been associated with stem cell properties. To analyze effects of cytotoxic chemotherapy on these cells, we examined a series of 50 breast carcinomas before and after neoadjuvant chemotherapy with epirubicin/cyclophosphamide using double immunofluorescence. Before treatment, an average of 4.4% of the tumor cells displayed a CD44(+)/CD24(-) phenotype. However, after chemotherapy, the frequency of CD44(+)/CD24(-) cells dropped to 2% (P = .008). To test this unexpected finding, we analyzed a second collective of 16 patients that preoperatively had received either 4 cycles of doxorubicin/pemetrexed, followed by 4 cycles of docetaxel or 4 cycles of doxorubicin/cyclophosphamide, followed by 4 cycles of docetaxel with similar results (8.7% CD44(+)/CD24(-) cells on average before and 1.1% after chemotherapy). In addition, no association was observed between the frequency of CD44(+)/CD24(-) cells and the response to chemotherapy or patient survival. However, patients with tumors containing high numbers of CD44(+)/CD24(-) cells more frequently developed bone metastases in the course of disease. In conclusion, our findings challenge the proposed role of CD44(+)/CD24(-) cells as cancer stem cells in tumor resistance to chemotherapy as they apparently are not selected by conventional cytotoxic agents.
Aulmann
Sebastian
S
Institute of Pathology, Heidelberg University, 69120 Heidelberg, Germany. sebastian.aulmann@med.uni-heidelberg.de
Waldburger
Nina
N
Penzel
Roland
R
Andrulis
Mindaugas
M
Schirmacher
Peter
P
Sinn
Hans Peter
HP
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism*; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005455:Fluorescent Antibody Technique; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D000068437:Pemetrexed; D043823:Taxoids / Q000008:administration & dosage
D051927:CD24 Antigen; D005971:Glutamates; D018960:Hyaluronan Receptors; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D015251:Epirubicin; D006147:Guanine; D004317:Doxorubicin; D003520:Cyclophosphamide