CD49f-positive cell population efficiently enriches colon cancer-initiating cells

Abstract

Abstract. Cancer stem cells (CSCs) also known as cancerinitiating cells (CICs) show high tumorigenic activity and high chemo-and radiation resistance. It is, therefore, important to identify CSCs reliably to develop novel curative cancer treatments. In this study, we re-evaluated CSC markers of colorectal cancer for their cellular differentiation and tumorigenic activity, with the aim to identify reliable CSC markers. The rates of change in CD44, CD133, CD166, CD24, CD49f and CXCR4 expression during sodium butyrate (NaBT)-induced cell differentiation were assessed in HT29 and Caco2 colon cancer cell lines. Expression levels of target markers were assessed in clinical CRC samples. Tumorigenic activity was assessed on isolated cell fractions identified by multicolor flow cytometric analysis. In the cell differentiation assay, the average percent change was higher in CD44 (-98.2%) and CD49f (-74.4%) compared to CD133 (-17.9%) and CD166 (-49.4%). Expression of CD24 and CXCR4 appeared random in HT29 and Caco2. Expression of CD44, CD49f, CD133 and CD166 was confirmed in all four clinical CRC samples. Limiting dilution assay of

Resistance to Taxanes in Triple-Negative Breast Cancer Associates with the Dynamics of a CD49f+ Tumor-Initiating Population

“…Previous reports have also shown the increased tumor-initiating ability of CD49f+ cells in breast and other solid tumors (Haraguchi et al., 2013, Lo et al., 2012, Meyer et al., 2010, Vassilopoulos et al., 2014). These findings do not imply that the CD49f+ cells are the CSC in TNBC, but demonstrate that the CD49f+ population is associated with taxane resistance.…”

Overexpression of Thy1 and ITGA6 is associated with invasion, metastasis and poor prognosis in human gallbladder carcinoma

“…Thus, identifying and characterizing the putative CSC population in solid tumors will not only contribute to our understanding of the mechanisms of tumor initiation, metastasis and recurrence, but will also aid in the development of novel CSC-targeting therapies. Both Thy1 and ITGA6 have been used for identifying CSCs in tumors of several tissue types, including the prostate gland (4,37,38), mammary gland (39), brain (23) and colon (40). In the diseased liver, Thy1 is expressed in hepatic stem cells, hepatic fibroblasts, myofibroblasts and tumor stroma, and in a small percentage of CSCs (5,6,41–43).…”

“…Therefore, efficient biomarkers are vital for identifying CSCs. Although the CSC theory is still controversial, CSCs have been identified in multiple solid tumors, including breast cancer (21), hepatocellular carcinoma (22), glioma (16), prostate cancer (4), colorectal cancer (23) and pancreatic cancer (24). However, whether there are CSCs in GBC is not clear.…”

Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance

“…Many of the same integrins that are enriched on normal adult stem and progenitor cells are also markers of CSCs, including integrin subunits β1, α6, and β3 [34]. Among these, α6 is the most widely observed, enriching for CSCs in breast [35], prostate [36], squamous cell carcinoma [37] and colorectal [38] cancers. Recent studies have also characterized integrin β4 as a new CSC marker in lung cancer, where it is involved in self-renewal, tumor propagation, and chemotherapy resistance [39].…”