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卵巢癌干细胞样侧群细胞具有致瘤性和化疗耐药性。

Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant.

机构信息

Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, 94143-0556, USA.

出版信息

Br J Cancer. 2010 Apr 13;102(8):1276-83. doi: 10.1038/sj.bjc.6605626. Epub 2010 Mar 30.

DOI:10.1038/sj.bjc.6605626
PMID:20354527
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2856005/
Abstract

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.

摘要

背景

卵巢癌是最致命的妇科恶性肿瘤。尽管卵巢癌患者最初通常对化疗有反应,但他们通常会产生耐药性。我们假设一小部分卵巢癌细胞具有促进肿瘤发生和耐药的干细胞样细胞特性。

方法

利用流式细胞术和 Hoechst 33342 外排分离来自卵巢癌患者腹水和接种人卵巢癌细胞系的小鼠的侧群(SP)细胞。通过免疫细胞化学和 RT-PCR 检查 SP 细胞中的干细胞标志物 OCT4、NANOG、STELLAR 和 ABCG2/BCRP1。研究 SP 细胞和非 SP 细胞在体外和体内的致瘤性和化疗耐药性。

结果

SP 细胞通过免疫细胞化学和 RT-PCR 表达 ABCG2/BCRP1、OCT4、STELLAR 和 NANOG。SP 细胞中的 ABCG2/BCRP1 表达高于非 SP 细胞。用 SP 细胞接种的异种小鼠比用非 SP 细胞接种的小鼠产生更多的肿瘤。平行地,SP 细胞培养导致广泛的细胞增殖,明显多于非 SP 细胞。SP 细胞对化疗的抵抗力比非 SP 细胞更强,无论是在体内还是在体外。

结论

卵巢癌 SP 细胞具有致瘤性和化疗耐药性。ABCG2/BCRP1 在化疗耐药中起重要作用,这对新的治疗方法具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/a486ac452c5d/6605626f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/70ff7e3f263a/6605626f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/2cdaae4e2541/6605626f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/b2771bd2ee12/6605626f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/7ee1994ab7da/6605626f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/a486ac452c5d/6605626f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/70ff7e3f263a/6605626f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/2cdaae4e2541/6605626f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/b2771bd2ee12/6605626f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/7ee1994ab7da/6605626f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd3/2856005/a486ac452c5d/6605626f5.jpg

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