In triple negative breast tumor cells, PLC-β2 promotes the conversion of CD133high to CD133low phenotype and reduces the CD133-related invasiveness

Abstract

BackgroundBeyond its possible correlation with stemness of tumor cells, CD133/prominin1 is considered an important marker in breast cancer, since it correlates with tumor size, metastasis and clinical stage of triple-negative breast cancers (TNBC), to date the highest risk breast neoplasia.MethodsTo study the correlation between the levels of CD133 expression and the biology of breast-derived cells, CD133low and CD133high cell subpopulations isolated from triple negative MDA-MB-231 cells were compared in terms of malignant properties and protein expression.ResultsHigh expression of CD133 characterizes cells with larger adhesion area, lower proliferation rate and reduced migration speed, indicative of a less undifferentiated phenotype. Conversely, when compared with CD133low cells, CD133high cells show higher invasive capability and increased expression of proteins involved in metastasis and drug-resistance of breast tumors. Among the signalling proteins examined, PLC-β2 expression inversely correlates with the levels of CD133 and has a role in inducing the CD133high cells to CD133low cells conversion, suggesting that, in TNBC cells, the de-regulation of this PLC isoform is responsible of the switch from an early to a mature tumoral phenotype also by reducing the expression of CD133.ConclusionsSince CD133 plays a role in determining the invasiveness of CD133high cells, it may constitute an attractive target to reduce the metastatic potential of TNBC. In addition, our data showing that the forced up-regulation of PLC-β2 counteracts the invasiveness of CD133-positive MDA-MB-231 cells might contribute to identify unexplored key steps responsible for the TNBC high malignancy, to be considered for potential therapeutic strategies.

Characterization of the expression of the pro-metastatic MenaINV isoform during breast tumor progression

“…Secondly, we examined Mena INV expression relative to two known stem cell markers in mouse PyMT tumors, ALDH and CD133, whose expression has been associated with stemness (Fig 6D). Indeed, recent studies have shown that cells expressing high levels of CD133 showed higher invasive potential and drug resistance, while cells that were ALDH- and CD133-positive were highly tumorigenic [25] [27]. As expected, we observed a positive correlation between CD133 and ALDH expression (Fig 6E); however, no significant association between cells expressing Mena INV and those expressing canonical stem cell markers.…”

HIF-1-alpha links mitochondrial perturbation to the dynamic acquisition of breast cancer tumorigenicity

“…These are cell surface markers frequently used to identify CSCs in BC [39–42]. Because more than 70% of MDA-MB-231 cells exhibit the CD44 High CD24 Low phenotype [39] and CD133 expression is highly correlated with the invasiveness and poor prognosis of triple-negative BC (TNBC) [40, 42], we assessed whether DKG treatment increased the surface expression of CD133 in MDA-MB-231 cells by flow cytometry. A 4-fold increase in the percentage of CD133-positive was observed in DKG-treated MDA-MB-231 cells (4 and 7 days; Figures 2B, panel a , and S2B).…”

Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

“…CD133, a transmembrane glycoprotein, is a more recent BCSC marker identified to be correlated with prognosis in breast cancer. Studies in vitro have proven that CD133 is suitable for enriching BCSCs in TNBC 22, 23. For CD133+ phenotype, some studies documented poor prognosis in TNBC 24, while others did not 25.…”