Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant
Autor: | C McArthur, R B Jaffe, L Hu |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Homeobox protein NANOG
Cancer Research Pathology medicine.medical_specialty ABCG2 Mice Nude Biology medicine.disease_cause Stem cell marker Mice Side population Cell Line Tumor medicine ovarian cancer stem-like cells ATP Binding Cassette Transporter Subfamily G Member 2 Animals Ascitic Fluid Humans Molecular Diagnostics Ovarian Neoplasms drug resistance Cancer medicine.disease Flow Cytometry Neoplasm Proteins Oncology Cell culture Drug Resistance Neoplasm embryonic structures tumourigenesis Cancer research Neoplastic Stem Cells ATP-Binding Cassette Transporters Female Stem cell side population Carcinogenesis Ovarian cancer Neoplasm Transplantation |
Zdroj: | British Journal of Cancer |
ISSN: | 1532-1827 0007-0920 |
Popis: | Background: Ovarian cancer is the most lethal gynaecological malignancy. Although ovarian cancer patients often respond initially to chemotherapy, they usually develop chemoresistance. We hypothesised that a small portion of ovarian cancer cells have stem-like cell properties that contribute to tumourigenesis and drug resistance. Methods: Flow cytometry and Hoechst 33342 efflux isolated side-population (SP) cells from ascites derived from ovarian cancer patients and from mice inoculated with human ovarian cancer cell lines. The SP cells were examined for stem cell markers OCT4, NANOG, STELLAR, and ABCG2/BCRP1 by immunocytochemistry and RT–PCR. The SP cells and non-SP cells were studied for tumourigenesis and chemoresistance in vitro and in vivo. Results: The SP cells expressed ABCG2/BCRP1, OCT4, STELLAR, and NANOG, detected by immunocytochemistry and RT–PCR. ABCG2/BCRP1 expression was higher in SP than in non-SP cells. Xenogeneic mice inoculated with SP cells yielded more tumours than did mice inoculated with non-SP cells. In parallel, SP cell culture resulted in extensive cell proliferation, which was markedly more than in non-SP cells. SP cells resisted chemotherapy compared with non-SP cells, both in vivo and in vitro. Conclusion: Ovarian cancer SP cells are tumourigenic and chemoresistant. ABCG2/BCRP1 has an important role in chemoresistance, which has implications for new therapeutic approaches. |
Databáze: | OpenAIRE |
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