The regulation of CD24 mRNA in MCF-7 cells by amino acid availability may play an important role in the progression and metastasis of human breast cancer.
One tumor had distinct features of EMT and gave rise to cell lines that contained a distinct CD44+/CD24-/low population that may correlate with human breast cancer stem cells.
Breast cancer cells expressing elevated levels of Aldehyde Dehydrogenase 1 (ALDH1) are also described as CSCs with ALDH1+/CD44+/CD24- subpopulation displaying highest tumorigenic potential in NOD/SCID models.
The side population (SP) and the CD44(+)/CD24(-/low) population have been reported in separate studies to include more tumorigenic cells than other populations, and to have the ability to form new tumors and undergo heterogeneous differentiation in breast cancer tissue.
ER-/PR-/HER2/neu + breast cancer cells were flow-sorted into subpopulations: (A) CD49f(+) CD24(-), (B) CD49f(+)CD24(+), (C) CD49f CD24(-), and (D) CD49f(-)CD24(+).
The findings of this study have implications in regard to the origins of (1) ER alpha-positive breast cancers, (2) CD44+/CD24-/low breast tumour stem cells and (3) the metastatic ability of breast cancer.
We showed that several breast cancer cell lines have a small population of CD24(-/low)/CD44(+) cells in which TICs may be enriched, and confirmed the properties of TICs in a xenograft model.
Taken together, our data demonstrate the direct involvement of Twist in generating a breast cancer stem cell phenotype through down-regulation of CD24 expression and independent of an epithelial-mesenchymal transition.
The basal-like/stemness type breast cancer cell line subpopulation MDA-MB-468 CD44high/CD24-/low, carrying high egfr amplifications, was chosen as a model system in this study.
Intrinsic genetic plasticity to efficiently drive the emergence of the CD44(pos)/CD24(neg/low) mesenchymal phenotype may account for de novo resistance to HER2 targeting therapies in basal-like BC carrying HER2 gene amplification.
SLUG, a mediator of the epithelial-mesenchymal transition process, is over-expressed in CD44(+)/CD24(-) tumor initiating breast cancer cells and in basal-like carcinoma, a subtype of aggressive breast cancer endowed with a stem cell-like gene expression profile.
Metformin treatment dynamically regulated the CD44(pos)CD24(neg/low) breast cancer stem cell immunophenotype, transcriptionally reprogrammed cells through decreased expression of key drivers of the EMT machinery including the transcription factors ZEB1, TWIST1 and SNAI2 (Slug) and the pleiotrophic cytokines TGFβs, and lastly impeded the propensity of breast cancer stem cells to form multicellular "microtumors" in non-adherent and non-differentiating conditions (i.e., "mammospheres").
Ectopic overexpression of uPAR in human MDA-MB-468 breast cancer cells promoted the emergence of a CD24(-)/CD44(+) phenotype, characteristic of CSCs, while increasing the cell surface abundance of integrin subunits β1/CD29 and α6/CD49f that represent putative mammary gland stem cell biomarkers. uPAR overexpression increased mammosphere formation in vitro and tumor formation in an immunocompromized severe combined immunodeficient (SCID) mouse model of orthotopic breast cancer.
In contrast, breast cancer CD44(+)/CD24(-/low) CIC have dysregulated innate immune responses featuring dysfunctional virus recognition caused by impaired trafficking of TLR9 and cofactor MyD88 and the absence of TLR2, having a deleterious impact on TLR pattern recognition receptor signaling.
Regardless the proportion of T-ICs, FACS-sorted CD44(+)/CD24(-) cells that derived from primary tumors or breast cancer lines were about 10-60 fold more resistant to chemotherapy relative to the non- CD44(+)/CD24(-) cells and their parental cells.
It has been suggested that breast cancer stem cells (CSCs), which characterized by CD44(+)CD24(-/low), may result in treatment failure in patients with breast cancer.
The expression levels of the three adhesion proteins were quantitatively different in the cell lines but the composite CD24(low/-)CD44(+)EpCAM(+) breast cancer stem cell phenotype was shown to exist as a small fraction, between 0.1% and 1.2%, in all breast cancer cell lines tested.