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A more recent version of this article appeared on August 1, 2008

Published online before print July 3, 2008
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Copyright © 2008 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2008.071214

Accepted for publication May 13, 2008.

Article

The Lymphovascular Embolus of Inflammatory Breast Cancer Expresses a Stem Cell-Like Phenotype

Yi Xiao, Yin Ye, Kurtis Yearsley, Susie Jones, and Sanford H. Barsky@

From the Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio

@ To whom correspondence should be addressed. E-mail: sanford.barsky{at}osumc.edu.


  Abstract

Inflammatory breast carcinoma (IBC) is a particularly lethal form of breast cancer characterized by exaggerated lymphovascular invasion, which is a phenotype recapitulated in our human xenograft MARY-X. MARY-X generated spheroids in vitro that resemble the embryonal blastocyst. Because of the resemblance of the spheroids to the embryonal blastocyst and their resistance to traditional chemotherapy/radiotherapy, we hypothesized that the spheroids expressed a stem cell-like phenotype. MARY-X spheroids expressed embryonal stem cell markers including stellar, rex-1, nestin, H19, and potent transcriptional factors, oct-4, nanog, and sox-2, which are associated with stem cell self-renewal and developmental potential. Most importantly, MARY-X spheroids expressed a cancer stem cell profile characterized by CD44+/CD24-/low, ALDH1, and most uniquely, CD133. A significant percentage of single cells of MARY-X exhibited distinct proliferative and morphogenic potencies in vitro. As few as 100 cells derived from single-cell clonogenic expansion were tumorigenic with recapitulation of the IBC phenotype. Prototype stem cell signaling pathways such as notch3 were active in MARY-X. The stem cell phenotype exhibited by MARY-X also was exhibited by the lymphovascular emboli of human IBC cases independent of their molecular subtype. This stem cell-like phenotype may contribute to the aggressive nature of IBC but also may lend itself to selective targeting.






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Copyright © 2008 by the American Society for Investigative Pathology.