CD133+ stem and/or progenitor‐like cells characterize the lymphovascular emboli of inflammatory breast carcinoma

As one of the most lethal forms of breast cancer, inflammatory breast carcinoma (IBC) is characterized by an exaggerated degree of lymphovascular invasion (LVI), a phenotype which is recapitulated within our human transplantable IBC xenograft, MARY‐X. This model exhibits florid LVI in vivo and corresponding spheroids in vitro . The spheroids contain a high percentage of CD133+ cells. These cells possess stem and/or progenitor cell‐like characteristics. Comparing MARY‐X with common non‐IBC breast carcinoma and normal cell lines (MDA‐MB‐468, MDA‐MB‐231, MCF‐7, HMEC), we found specific markers (Stellar, H19, Rex‐1, Nestin) known to be associated with embryonal or neural stem and/or progenitor cells highly expressed within the spheroids of MARY‐X. In addition, RT‐PCR analyses of MARY‐X also revealed the expression of OCT4, SOX2, and Nanog, transcriptional determinants essential for the pluripotency and self‐renewal of human embryonal stem cells. Most importantly, CD133, a surface marker for human leukemic stem cells and human brain tumor stem cells, was also strongly expressed on the spheroids of MARY‐X but not on the other non‐IBC cell lines. Interestingly, only the CD133+ subpopulation of MARY‐X expressed both the stem cell transcriptional determinants mentioned previously as well as the capacity for self‐renewal and tumorigenicity. These findings suggest that MARY‐X and therefore IBC naturally contain within their lymphovascular emboli a high percentage of CD133+ cells, cells which exhibit stem and/or progenitor cell‐like markers and characteristics which, in turn, may account for the biological aggressive behavior of IBC. This study was supported by The Donald A. Senhauser Endowment.