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

By C. Sheridan, H. Kishimoto, R. Fuchs, S. Mehrotra, P. Bhat-Nakshatri, Charles H. Turner, R. Goulet, S. Badve, Harikrishna Nakshatri. Breast Cancer Research, 2006

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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.

Subfields: Cell Biology, Oncology, Psychiatry and Mental health

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Citations in the corpus

Bicarbonate Increases Tumor pH and Inhibits Spontaneous Metastases (2009, background): “Notably, CD44 is associated with breast cancer cells with stem cell–like properties, and these are noted for being resistant to environmentally induced apoptosis (42, 43).”
Breast Cancer Stem Cells Transition between Epithelial and Mesenchymal States Reflective of their Normal Counterparts (2013, result): “This model is also supported by studies demonstrating that in patients with metastatic breast cancer, circulating tumor cells and bone marrow micrometastasis are highly enriched for cells expressing the EMT BCSC marker CD24 CD44+ (Sheridan et al., 2006).”
IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. (2007, background): “Accordingly, it has been shown that IL-6 gene expression is high in breast cancer cell lines enriched in CD44+CD24– invasive cells (16).”
DeepST: identifying spatial domains in spatial transcriptomics by deep learning (2022, background): “AZGP1 levels dictate the histologic grade of breast cancer tumours in domain 1 (45), whereas ART3 and CD24 are key triple-negative breast cancer indicators (Figure 4I) (46–49).”
Deconstructing the molecular portraits of breast cancer (2010, result): “This is in concordance with two other reports (Fillmore and Kuperwasser, 2008; Sheridan et al., 2006) that showed that the MDA-MB231, SUM159PT, SUM1315 MDA-MB436, Hs578T and HBL100 cell lines have a high proportion (>90”
Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy (2008, background): “In light of recent studies that suggest that presence of CD44+/CD24- cells does not correlate with clinical outcome [33] or with distant metastasis [17], we also found that cell lines with few CD44+/ CD24- cells were not necessarily less tumorigenic than cell lines with very high numbers of CD44+/CD”
HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion (2008, background): “It has been suggested that tumor invasion and metastasis may be mediated by the cancer stem cell population (Sheridan et al., 2006; Wicha et al., 2006).”