Sheridan Carol, Kishimoto Hiromitsu, Fuchs Robyn K, Mehrotra Sanjana, Bhat-Nakshatri Poornima, Turner Charles H, Goulet Robert, Badve Sunil, Nakshatri Harikrishna
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Breast Cancer Res. 2006;8(5):R59. doi: 10.1186/bcr1610.
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-1alpha, 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.
据报道，乳腺癌细胞的一个亚群（CD44+/CD24-）具有干细胞/祖细胞特性。本研究的目的是调查该癌细胞亚群是否具有在转移部位侵袭、归巢和增殖的独特能力。
通过流式细胞术测定CD44和CD24的表达。采用Northern印迹法测定促侵袭和“骨与肺转移特征”基因的表达。分别使用基质胶侵袭试验和向裸鼠心内接种来评估侵袭、转移部位的归巢和增殖情况。
在检测的13个乳腺癌细胞系中（MDA-MB-231、MDA-MB-436、Hs578T、SUM1315和HBL-100），有5个含有较高比例（>30%）的CD44+/CD24-细胞。CD44+/CD24-细胞数量多的细胞系表达基底/间充质或肌上皮标志物，但不表达腔上皮标志物。具有显著CD44+/CD24-群体的细胞系中，促侵袭基因（IL-1α、IL-6、IL-8和尿激酶型纤溶酶原激活剂[UPA]）的表达水平高于其他细胞系。在CD44+/CD24(-)阳性细胞系中，MDA-MB-231具有独特的特性，即表达多种有利于骨和肺转移的基因。与之前在裸鼠中的研究一致，具有CD44+/CD24-亚群的细胞系比其他细胞系更具侵袭性。然而，只有一部分CD44+/CD24(-)阳性细胞系能够在肺中归巢和增殖。
具有CD44+/CD24-亚群的乳腺癌细胞表达更高水平的促侵袭基因，具有高度侵袭性。然而，这种表型不足以预测肺转移能力。
