Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features

• DOI: 10.1073/pnas.0905718106
• Publication Date: 2009-08-04T01:43:30Z
• Authors: Chad J. Creighton; Xiaoxian Li; Melissa Landis; J. Michael Dixon; Veronique M. Neum...; Ashley Sjolund; David L. Rimm; Helen Wong; Angel Rodriguez; Jason I. Herschko...; Cheng Fan; Xiaomei Zhang; Xiaping He; Anne Pavlick; M. Carolina Gutie...; Lorna Renshaw; Alexey A. Larionov; Dana Faratian; Susan G. Hilsenbeck; Charles M. Perou; Michael T. Lewis; Jeffrey M. Rosen; Jenny C. Chang
• Keywords: CD24

Some breast cancers have been shown to contain a small fraction of cells characterized by CD44(+)/CD24(-/low) cell-surface antigen profile that high tumor-initiating potential. In addition, cancer propagated in vitro as mammospheres (MSs) also be enriched for capable self-renewal. this study, we defined gene expression signature common both and MS-forming cells. To examine its clinical significance, determined whether tumor surviving after conventional treatments were bearing CD44(+)/CD24(-/low)-MS signature. The was found mainly human tumors the recently identified "claudin-low" molecular subtype, which is many epithelial-mesenchymal-transition (EMT)-associated genes. Both claudin-low signatures more pronounced tissue remaining either endocrine therapy (letrozole) or chemotherapy (docetaxel), consistent with selective survival posttreatment. We confirmed an increased mesenchymal markers, including vimentin (VIM) cytokeratin-positive epithelial metalloproteinase 2 (MMP2), two separate sets postletrozole vs. pretreatment specimens. Taken together, these data provide supporting evidence residual cell populations treatment may subpopulations features. Targeting proteins involved EMT therapeutic strategy eliminating prevent recurrence improve long-term patients.