CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis.

CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis.
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DOI:
10.1186/bcr1610
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发表时间:
2006
影响因子:
7.4
通讯作者:
Nakshatri, Harikrishna
Nakshatri, Harikrishna
中科院分区:
医学1区
文献类型:
--
作者:
Sheridan, Carol;Kishimoto, Hiromitsu;Fuchs, Robyn K.;Mehrotra, Sanjana;Bhat-Nakshatri, Poornima;Turner, Charles H.;Goulet, Robert, Jr.;Badve, Sunil;Nakshatri, Harikrishna

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据报道,乳腺癌细胞的亚群(CD 44 +/CD 24-)具有干/祖细胞特性。本研究的目的是调查这种癌细胞亚群是否具有独特的侵袭、归巢和在转移部位增殖的能力。流式细胞术测定CD 44和CD 24表达。采用北方印迹法测定促侵袭基因和“骨和肺转移标记”基因的表达。基质胶侵袭试验和心内接种到裸鼠分别用于评估侵袭,和归巢和增殖在转移部位。在检查的13种乳腺癌细胞系中,有5种(MDA-MB-231、MDA-MB-436、Hs 578 T、SUM 1315和HBL-100)含有较高百分比(>30%)的CD 44 +/CD 24-细胞。具有高CD 44 +/CD 24-细胞数的细胞系表达基底/间充质或肌上皮标记物,但不表达管腔标记物。在具有显著CD 44 +/CD 24-群体的细胞系中,促侵袭基因(IL-1α、IL-6、IL-8和尿激酶纤溶酶原激活物[UPA])的表达水平高于其他细胞系。在CD 44 +/CD 24-阳性细胞系中,MDA-MB-231具有表达有利于骨和肺转移的广泛基因的独特性质。与先前在裸鼠中的研究一致,具有CD 44 +/CD 24-亚群的细胞系比其他细胞系更具侵袭性。然而,只有一个子集的CD 44 +/CD 24-阳性细胞系能够在肺中的家园和增殖。具有CD 44 +/CD 24-亚群的乳腺癌细胞表达更高水平的促侵袭基因,并且具有高度侵袭性。然而,这种表型不足以预测肺转移的能力。
A subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells has the unique ability to invade, home, and proliferate at sites of metastasis. CD44 and CD24 expression was determined by flow cytometry. Northern blotting was used to determine the expression of proinvasive and 'bone and lung metastasis signature' genes. A matrigel invasion assay and intracardiac inoculation into nude mice were used to evaluate invasion, and homing and proliferation at sites of metastasis, respectively. Five among 13 breast cancer cell lines examined (MDA-MB-231, MDA-MB-436, Hs578T, SUM1315, and HBL-100) contained a higher percentage (>30%) of CD44+/CD24- cells. Cell lines with high CD44+/CD24- cell numbers express basal/mesenchymal or myoepithelial but not luminal markers. Expression levels of proinvasive genes (IL-1α, IL-6, IL-8, and urokinase plasminogen activator [UPA]) were higher in cell lines with a significant CD44+/CD24- population than in other cell lines. Among the CD44+/CD24--positive cell lines, MDA-MB-231 has the unique property of expressing a broad range of genes that favor bone and lung metastasis. Consistent with previous studies in nude mice, cell lines with CD44+/CD24- subpopulation were more invasive than other cell lines. However, only a subset of CD44+/CD24--positive cell lines was able to home and proliferate in lungs. Breast cancer cells with CD44+/CD24- subpopulation express higher levels of proinvasive genes and have highly invasive properties. However, this phenotype is not sufficient to predict capacity for pulmonary metastasis.
DOI: 10.1158/0008-5472.can-04-1408
发表时间: 2005-07-15
期刊: CANCER RESEARCH
影响因子: 11.2
作者:
Kuperwasser, C;Dessain, S;Rosenblatt, M
通讯作者: Rosenblatt, M
DOI: 10.1074/jbc.m300609200
发表时间: 2003-06-13
影响因子: 4.8
作者:
Helbig, G;Christopherson, KW;Nakshatri, H
通讯作者: Nakshatri, H
DOI: 10.1038/nature04524
发表时间: 2006-03-30
期刊: NATURE
影响因子: 64.8
作者:
Jones, DH;Nakashima, T;Penninger, JM
通讯作者: Penninger, JM
DOI: 10.1023/a:1011371523994
发表时间: 2001-07-01
影响因子: 2.5
作者:
Bourguignon, LYW
通讯作者: Bourguignon, LYW
DOI: 10.1158/0008-5472.can-05-0619
发表时间: 2005-12-01
期刊: CANCER RESEARCH
影响因子: 11.2
作者:
Baumann, P;Cremers, N;Sleeman, JP
通讯作者: Sleeman, JP