Emergence of CD26+ Cancer Stem Cells with Metastatic Properties in Colorectal Carcinogenesis

Abstract

Colorectal cancer results from genetic aberrations which accumulate over a long period of time, with malignant and metastatic properties acquired at a relatively late stage. A subpopulation of CD26+ colorectal cancer stem cells are known to be implicated in metastasis. We quantified CD26+ cancer cells in 11 primary tumor samples by flow cytometry, and showed that tumors having confirmed or suspected metastases harbored a relatively high CD26+ level in these samples. We hypothesized that this subpopulation of cancer stem cells arises in the late stage of carcinogenesis from the bulk of tumor daughter cells which are CD26−. The manipulation of PIK3CA and TP53, two genes commonly deregulated in the late stage, had an effect on the maintenance of the CD26+ cell population. When CD26− tumor daughter cells were sorted and cultured, the emergence of tumor spheres containing CD26+ cells occurred. These findings shed light to the origin of colorectal cancer stem cells with metastatic properties, which has an implication on conventional treatments by surgery or adjuvant chemotherapy for tumor debulking.

Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells

“…This study suggests that the analysis of CSC subsets in the primary colon cancers according to CD26 expression may have important clinical implications as a selection criterion for adjuvant therapy. CD26 expression in colorectal cancers is observed particularly at late stages of tumor development and implies the emergence of a tumor cell population endowed with metastatic potential [ 383 ]. The CD26 + tumor cell population is maintained by genetic alterations at the level of TP53 and PIK3CA [ 383 ].…”

“…CD26 expression in colorectal cancers is observed particularly at late stages of tumor development and implies the emergence of a tumor cell population endowed with metastatic potential [ 383 ]. The CD26 + tumor cell population is maintained by genetic alterations at the level of TP53 and PIK3CA [ 383 ]. In vitro studies have shown the generation of CD26 + cells from CD26 − cells [ 383 ].…”

“…The CD26 + tumor cell population is maintained by genetic alterations at the level of TP53 and PIK3CA [ 383 ]. In vitro studies have shown the generation of CD26 + cells from CD26 − cells [ 383 ].…”

Targeting the Adenosinergic Axis in Chronic Lymphocytic Leukemia: A Way to Disrupt the Tumor Niche?

“…Deamination to inosine is mediated by ADA, an enzyme generally present in the cytoplasm but that can be localized on the cell surface when bound to anchoring proteins, such as CD26 [ 62 ]. CD26 plays a significant role in CLL biology, being both a disease marker and a modifier of tumor pathogenesis and development [ 63 , 64 , 65 , 66 ]. Several studies highlighted that expression of CD26 identifies CLL patients with high-risk of disease progression and treatment requirement [ 67 ].…”

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

“…The aim of this study was to test candidate CSC and MetSC markers in a panel of eight cell lines obtained from primary or metastatic tumors of patients in different disease stages [so that epithelial-mesenchymal transition (EMT) markers were also used]. The results would provide a functional characterization of specific cell subsets found in clinical specimens (Lieto et al, 2015; Cheung et al, 2017) and the possibility of using these chemo-resistant cells as targets for the development of new therapies.…”