Abstract
ABSTRACTTaking advantage of eight established cell lines from colorectal cancer patients at different stages of the disease and the fact that all of them could form spheres, cell surface biomarkers of cancer stem cells and epithelial-mesenchymal transition were tested. The aim was to investigate cancer stem cells and metastatic stem cells in order to provide functional characterization of circulating tumor cells and promote the development of new anti-metastatic therapies. Our model showed an important heterogeneity in EpCAM, CD133, CD44, LGR5, CD26 and E-cadherin expression. We showed the presence of a subset of E-cadherin+ (some cells being E-cadherinhigh) expressing CD26+ (or CD26high) together with the well-known CSC markers LGR5 and EpCAMhigh, sometimes in the absence of CD44 or CD133. The already described CD26+/E-cadherinlow or negative and CD26+/EpCAM−/CD133− subsets were also present. Cell division drastically affected the expression of all markers, in particular E-cadherin, so new-born cells resembled mesenchymal cells in surface staining. CD26 and/or dipeptidyl peptidase 4 inhibitors have already shown anti-metastatic effects in pre-clinical models, and the existence of these CD26+ subsets may help further research against cancer metastasis.
Highlights
Expression of stem cell, Cancer stem cells (CSCs) and epithelialmesenchymal transition (EMT) markers in colorectal cancer (CRC) cell lines The stem cell, CSC and EMT marker expression profile in eight CRC cell lines was analyzed by flow cytometry (Table 1), western blotting (Fig. 1A) and immunofluorescence (Fig. 1B–D)
We show for the first time that LGR5+, E-cadherinhigh, EpCAMhigh and CD26high are frequently associated in sphere-derived cells, that CD133 seems to be related to a different germinal line, and that cell division affects the expression of all markers, including that of E-cadherin
These results are highlighted with the recent report that has shown that LGR5+ cells are more important for the process of metastasis than for primary tumor growth
Summary
Metastasis accounts for the vast majority of deaths due to cancer because even if the primary tumor has been perfectly removed by surgery, tumor cells can have disseminated and established themselves in distant locations (Oskarsson et al, 2014; Pantel et al, 2008; Liu et al, 2014a,b; Miranda-Lorenzo et al, 2014; Driessens et al, 2012). Cancer stem cells (CSCs) are the only tumor cell type with long-term self-renewal potential because of their microenvironmental niche (Oskarsson et al, 2014; Liu et al, 2014a, b; Miranda-Lorenzo et al, 2014), suggesting that metastatic stem. An important question is which markers should be used for CSC and MetSC characterization
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