Research article

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

Carol Sheridan¹ , Hiromitsu Kishimoto¹ , Robyn K Fuchs² , Sanjana Mehrotra³ , Poornima Bhat-Nakshatri^4,5 , Charles H Turner⁶ , Robert Goulet Jr¹ , Sunil Badve³ and Harikrishna Nakshatri^1,4,5,7

¹Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA

²Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

³Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

⁴Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA

⁵Walther Cancer Institute, Indianapolis, IN 46208, USA

⁶Orthopedics Research Labs, Indiana University School of Medicine, Indianapolis, IN 46202, USA

⁷Department Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

author email corresponding author email

Breast Cancer Research 2006, 8:R59doi:10.1186/bcr1610

Published:	24 October 2006

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.