Abstract
IntroductionA 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.MethodsCD44 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.ResultsFive 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.ConclusionBreast 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.
Highlights
A subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties
Human breast cancer cell lines differ quantitatively in the proportion of CD44+/CD24- cells To test the hypothesis that human breast cancer cell lines differ in the proportion of CD44+/CD24- cells, we characterized 13 breast cancer cell lines by flow cytometry for surface expression of CD44 and CD24
In this report we show the relationship between CD44+/ CD24- phenotype of breast cancer cells and discrete steps of the metastatic cascade
Summary
A subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. Several studies implicated a subset of human breast cancer cells as having enhanced ability to form tumors in immunocompromised mice [9,10]. This subpopulation of cells demonstrated a capacity for self-renewal and generation of ADAMTS = a disintegrin and metalloproteinase with thrombospondin; CTGF = connective tissue growth factor; CXCR = CXC chemokine receptor; DMEM = Dulbecco's modified eagle medium; ER = estrogen receptor; FCS = fetal calf serum; IL = interleukin; MMP = matrix metalloproteinases; PBS = phosphate-buffered saline; RANK = receptor activator of nuclear factor-κB; RT-PCR = reverse transcriptase polymerase chain reaction; UPA = urokinase plasminogen activator. The potential of these tumorigenic stem/progenitor cells to establish metastasis is not known
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