CD133-positive cancer stem cells from colo205 human colon adenocarcinoma cell line show resistance to chemotherapy and display a specific metabolomic profile

Abstract

During the past decade, cancer stem-like cells (CSCs) have drawn substantial interest in cancer research since they have been described as major targets to improve treatment of tumors and to prevent recurrence and metastasis. In this paper, we report on the search for CSCs within the Colo205 human adenocarcinoma cell line. We describe that CD133 (prominin) was the only reliable marker for the isolation and characterization of CSCs within a Colo205 cell population. CD133-positive cells displayed many CSC characteristics, such as tumorsphere formation ability, expression of early-stage development markers, high invasiveness, raised tumor initiation potential and resistance to cisplatin chemotherapy treatment. In vitro analyses also highlighted a specific metabolomic profile of CD133-positive cells and we concluded that the chemotherapy resistance of CSCs could be related to the quiescence of such cells associated with their reduced metabolism. Furthermore, in vivo metabolome analyses suggested that a high level of circulating glutathione molecules could also promote treatment resistance. From the perspective of metabolomics, we also discuss the controversial use of serum-free in vitro cultures for CSC enrichment prior to further phenotype characterization.

Expression of CD133 in endometrial cancer cells and its implications

“…It was found that CD133+ cells could grow tumors in all three xenografted NOD-SCID mice with 1.5 × 10 5 cells but not CD133- cells. This finding is consistent with previous reports on colon cancer 49 and glioblastoma multiforme 50 . CSCs were found in CD133+ fractions of EC.…”

Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines

“…CD133 was recently reported as a promising CSC marker noted in prostate cancer ( 35 – 37 ), brain tumours ( 38 – 41 ), colon cancer ( 42 – 44 ) and hepatic carcinoma ( 45 – 48 ). However, in the context of lung cancer stem cells, the utility of the marker appears limited due to the low expression detected in most lung cancer samples ( 49 , 50 ), and the discrepancy of the findings in regards to CD133 in most studies have questioned the prognostic value of this marker in clinical application ( 50 – 52 ).…”

OVCAR-3 Spheroid-Derived Cells Display Distinct Metabolic Profiles

“…However, to date metabolomics has rarely been exploited to study cancer stem cells. To our knowledge, the only reported applications of metabolomics in this context was its use to study the differences between tumors derived from fresh glioma stem cells and cultured glioma stem cells in vivo using nuclear magnetic resonance spectroscopy [ 16 ], a recently published report on breast cancer stem cells’ reliance on glycolysis [ 17 ], and recent isolation of a colon cancer stem cell line with metabolomic characterization [ 18 ]. There is also increasing recent interest in cancer stem cell metabolism through approaches other than metabolomics, with many of the discoveries focused on enhanced glycolysis [ 19 – 30 ].…”