Surface expression marker profile in colon cancer cell lines and sphere-derived cells suggests complexity in CD26+cancer stem cells subsets

Abstract

Taking 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-cadherin high ) expressing CD26 + (or CD26 high ) together with the well-known CSC markers LGR5 and EpCAM high , sometimes in the absence of CD44 or CD133. The already described CD26 + /E-cadherin low 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.

Molecular features and gene expression signature of metastatic colorectal cancer (Review)

“…Commonly used CRC cell lines show that a percentage of stem cells from intestinal origin (as indicated by LGR5 expression from 1–22.5% and frequency of EpCAM + cells) is high in fully differentiated carcinoma cells. Sphere-derived cells showed enhanced frequencies (2- to 3-fold) of LGR5 positivity compared to the original cell lines ( 79 ). LGR5 + , E-cadherin high, EpCAM high and CD26 high are frequently associated with sphere-derived cells.…”

The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation

“…Another difficulty for differentiation-based studies is that most available intestinal cell models display very limited differentiation potential and no multipotency, HT29 cells being the exception since these cells can give rise to both absorptive and goblet cells, the two main intestinal cell types [ 1 ], under certain conditions [ 42 , 43 , 44 ]. Furthermore, HT29 cells are well characterized for their stem-like cell subpopulation [ 41 ].…”

“…In this study, we used the multipotent intestinal cell line HT29 to further investigate the involvement of the Hippo pathway on the differentiation of human absorptive and secretory intestinal lineages. Indeed, HT29 cells exhibit the unique ability to grow under normal conditions as a multilayer of undifferentiated cells which, similar to other cancer cell lines, contains stem-like cells [41] that have the potential to differentiate into absorptive and/or goblet cells under specific conditions [42][43][44].…”

The mechanism of sitagliptin inhibition of colorectal cancer cell lines' metastatic functionalities

“…After washing with sorting buffer, cells were sorted in a FACS Aria IIu analyser (BD Biosciences) using the PC FACS Diva software programme (BD Biosciences). Gating strategies for the cell lines have been previously explained in detail 10 . Each characterisation was repeated at least three times to validate the results observed.…”

“…CD26 (dipeptidyl peptidase IV, DPP4, EC 3.3.14.5) was recently identified as a marker of CSCs in several types of cancer 2–9 . In colorectal cancer (CRC), it identifies subsets of CSCs that could correspond to metastatic stem cells 6,10 . In fact, CD26 expression is associated in CRC with tumour malignant stages, the presence of distant metastasis, and worse prognosis 8,11,12 …”