Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy.
Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy.
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DOI：
10.1186/bcr1982
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发表时间：
2008
影响因子：
7.4
通讯作者：
Kuperwasser, Charlotte
中科院分区：
文献类型：
--
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
启动人类乳腺肿瘤的细胞（癌症干细胞）和构成肿瘤块的细胞之间的表型和功能差异难以仅使用原发性肿瘤组织进行研究。我们开始这项研究假设，乳腺癌细胞系将包含类似的分层分化程序中发现的原发性乳腺肿瘤。使用流式细胞术分析8种人乳腺细胞系（人乳腺上皮细胞和MCF 10A、MCF 7、SUM 149、SUM 159、SUM 1315和MDA.MB.231细胞）的CD 44、CD 24和上皮特异性抗原（ESA）表达。有限稀释原位注射用于评估肿瘤起始，同时进行系列集落形成单位、重建和肿瘤球测定以评估自我更新和分化。脉冲追踪溴脱氧尿苷（5-溴-2-脱氧尿苷[BrdU]）标记用于检测肿瘤干细胞的细胞周期和标记保留。用紫杉醇和5-氟尿嘧啶处理细胞以测试对化疗的选择性抗性，并检测化疗后的基因表达谱。细胞系中CD 44 +/CD 24-细胞的百分比与致瘤性无关，但当按CD 44 +/CD 24-/低/ESA+分选时，少至100个细胞即可形成肿瘤。此外，CD 44 +/CD 24-/ESA+细胞可以自我更新，重建亲本细胞系，保留BrdU标记，并优先在化疗中存活。这些数据验证了使用癌细胞系作为用于开发和测试旨在根除癌症干细胞的新型疗法的模型。
The phenotypic and functional differences between cells that initiate human breast tumors (cancer stem cells) and those that comprise the tumor bulk are difficult to study using only primary tumor tissue. We embarked on this study hypothesizing that breast cancer cell lines would contain analogous hierarchical differentiation programs to those found in primary breast tumors. Eight human breast cell lines (human mammary epithelial cells, and MCF10A, MCF7, SUM149, SUM159, SUM1315 and MDA.MB.231 cells) were analyzed using flow cytometry for CD44, CD24, and epithelial-specific antigen (ESA) expression. Limiting dilution orthotopic injections were used to evaluate tumor initiation, while serial colony-forming unit, reconstitution and tumorsphere assays were performed to assess self-renewal and differentiation. Pulse-chase bromodeoxyuridine (5-bromo-2-deoxyuridine [BrdU]) labeling was used to examine cell cycle and label-retention of cancer stem cells. Cells were treated with paclitaxol and 5-fluorouracil to test selective resistance to chemotherapy, and gene expression profile after chemotherapy were examined. The percentage of CD44+/CD24- cells within cell lines does not correlate with tumorigenicity, but as few as 100 cells can form tumors when sorted for CD44+/CD24-/low/ESA+. Furthermore, CD44+/CD24-/ESA+ cells can self-renew, reconstitute the parental cell line, retain BrdU label, and preferentially survive chemotherapy. These data validate the use of cancer cell lines as models for the development and testing of novel therapeutics aimed at eradicating cancer stem cells.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
7.4
作者：
Sheridan, Carol;Kishimoto, Hiromitsu;Fuchs, Robyn K.;Mehrotra, Sanjana;Bhat-Nakshatri, Poornima;Turner, Charles H.;Goulet, Robert, Jr.;Badve, Sunil;Nakshatri, Harikrishna
通讯作者：
Nakshatri, Harikrishna
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
11.2
作者：
Kuperwasser, C;Dessain, S;Rosenblatt, M
通讯作者：
Rosenblatt, M
影响因子：
50.3
作者：
Neve, Richard M.;Chin, Koei;Gray, Joe W.
通讯作者：
Gray, Joe W.