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

• Authors: Carol Sheridan, Indiana University; Hiromitsu Kishimoto, Indiana University; Robyn K. Fuchs, Indiana University; Sanjana Mehrotra, Indiana University; Poornima Bhat-Nakshatri, Indiana University; Charles H. Turner, Indiana University; Robert Goulet, Jr., Indiana University; Sunil Badve, Emory University; Harikrishna Nakshatri, Indiana University
• Journal Title: BREAST CANCER RESEARCH
• Volume: Volume 8, Number 5
• Publisher: BMC | 2006-01-01, Pages R59-R59
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1186/bcr1610
• Subjects: Health Sciences, Oncology; Health Sciences, Obstetrics and Gynecology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; ESTROGEN-RECEPTOR; BONE METASTASIS; MAMMARY-GLAND; EXPRESSION; LINES; ACTIVATION; MIGRATION; TUMORS; PROGRESSION; VIMENTIN

Abstract

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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. © 2006 Sheridan et al., licensee BioMed Central Ltd.