Cancer stem cell markers ALDH1 and CD44+/CD24- phenotype and their prognosis impact in invasive ductal carcinoma

Abstract

Breast cancer is a very heterogeneous disease. The intrinsic molecular subtypes can explain the intertumoral heterogeneity and the cancer stem cell (CSC) hypothesis can explain the intratumoral heterogeneity of this kind of tumor. CD44+/CD24- phenotype and ALDH1 expression are the major CSC markers described in invasive breast cancer. In the present study, 144 samples of invasive breast carcinoma, no special type were distributed in 15 tissue microarrays (TMA) and then evaluated for expression of the CD44+/CD24- phenotype and ALDH1 to understand the importance of these CSC markers and the clinical aspects of breast cancer. The samples were classified into four molecular subtypes according to clinicopathological criteria: Luminal A, Luminal B, HER2, and Basal-like. A statistical association was found between the molecular subtypes and the CSC markers, with HER2 the most frequent subtype for both markers. ALDH1 was also associated with other poor prognostic variables, such as a high histological grade and larger tumors, but it was not associated with the patients’ prognosis in this sample and nor was the CD44+/CD24- phenotype in a multivariate analysis. There are still many controversies about the role of these markers in breast cancer molecular subtypes. The identification of these populations of cells, through immunohistochemical markers, can help to better understand the CSC theory in clinical practice and, in the near future, contribute to developing new target therapies.

Sorafenib Inhibits Proliferation, Migration and Invasion of Breast Cancer Cells

“…3a, b). The cancer stem cells in breast cancer is defined by CD44 + / CD24 -/lo and CD49F expressing cells [23,24]. On treatment with sorafenib, we found a significant increase in CD24 expression in MDA-MB-231 cells indicating a reduction in the breast cancer stem cell population (Fig.…”

“…CD24 expression, which inhibits stemness in breast cancer cells [31], was upregulated, whereas CD44, which promotes stemness, was downregulated upon sorafenib treatment. However, sorafenib did not affect the expression of ALDH1A3, a marker that in combination with CD44 and CD24 expression identifies breast cancer stem cells [23]. Nevertheless, CD49F, a breast cancer stem cell marker [32] and an indicator of metastasis [32], was downregulated on sorafenib treatment, again, suggesting its anti-metastatic effect.…”

“…The proliferation, progression and metastatic properties of cancer cells is mediated by cancer stem cells in several cancer types including the breast cancer [23]; therefore, we explored the effect of sorafenib on breast cancer stem cells and self-renewal properties. We found a significant decrease in the self-renewal ability of both MCF7 and MDA-MB-231 cells after sorafenib treatment as determined by colony formation assay (Fig.…”

“…Ha et al [28] and Yoshida et al [29] reported similar inhibition of migration and invasion in hepatocellular carcinoma cells after sorafenib treatment. In association with reduced migration and in- Breast cancer stem cells, responsible for cancer initiation, progression, chemoresistance and recurrence were identified as CD44 + /CD24 -/lo along with other markers such ALDH and CD49F [23,24,30]. CD44 + /CD24 -/lo phenotype is enriched in basal like breast cancer and the majority of MDA-MB-231 cells have CD44 + /CD24 -/lo phenotype.…”

miRNAs as radio‐response biomarkers for breast cancer stem cells

“…Cell surface marker levels of CSCs were determined with human antibodies anti‐CD44‐PE and anti‐CD24‐APC (Miltenyi Biotec, Auburn, CA, USA) and ALDEFLUOR assay (Stem Cell Technologies) to detect enzyme ALDH1 activity was performed to complete characterization (Li et al , ; Rabinovich et al , ; Wang et al , ). Samples were measured and analyzed by flow cytometry on a FACS CANTO II (BD Biosciences, San Jose, CA, USA).…”