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2015 ; 95
(1
): 100-12
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Methods for detecting circulating cancer stem cells (CCSCs) as a novel approach
for diagnosis of colon cancer relapse/metastasis
#MMPMID25347154
Kantara C
; O'Connell MR
; Luthra G
; Gajjar A
; Sarkar S
; Ullrich RL
; Singh P
Lab Invest
2015[Jan]; 95
(1
): 100-12
PMID25347154
show ga
Cancer stem cells (CSCs) are believed to be resistant to currently available
therapies and may be responsible for relapse of cancer in patients. Measuring
circulating tumor cells (CTCs) in the blood of patients has emerged as a
non-invasive diagnostic procedure for screening patients who may be at high risk
for developing metastatic cancers or relapse of the cancer disease. However,
accurate detection of CTCs has remained a problem, as epithelial-cell markers
used to date are not always reliable for detecting CTCs, especially during
epithelial-mesenchymal transition. As CSCs are required to initiate metastatic
tumors, our goal was to optimize and standardize a method for identifying
circulating CSCs (CCSCs) in patients, using established CSC markers. Here, we
report for the first time the detection of CCSCs in the blood of athymic nude
mice, bearing metastatic tumors, and in the blood of patients positive for
colonic adenocarcinomas. Using a simple and non-expensive method, we isolated a
relatively pure population of CSCs (CD45-/CK19+), free of red blood cells and
largely free of contaminating CD45+ white blood cells. Enriched CCSCs from
patients with colon adenocarcinomas had a malignant phenotype and co-expressed
CSC markers (DCLK1/LGR5) with CD44/Annexin A2. CSCs were not found in the blood
of non-cancer patients, free of colonic growths. Enriched CCSCs from colon cancer
patients grew primary spheroids, suggesting the presence of tumor-initiating
cells in the blood of these patients. In conclusion, we have developed a novel
diagnostic assay for detecting CSCs in circulation, which may more accurately
predict the risk of relapse or metastatic disease in patients. As CSCs can
potentially initiate metastatic growths, patients positive for CCSCs can be
treated with inhibitory agents that selectively target CSCs, besides conventional
treatments, to reduce the risk of relapse/metastatic disease for improving
clinical outcomes.