The lymphovascular embolus of inflammatory breast cancer expresses a stem cell-like phenotype

被引:94
作者
Xiao, Yi [1 ]
Ye, Yin [1 ]
Yearsley, Kurtis [1 ]
Jones, Susie [1 ]
Barsky, Sanford H. [1 ]
机构
[1] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA
关键词
D O I
10.2353/ajpath.2008.071214
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页码:561 / 574
页数:14
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