In:
Cancer Science, Wiley, Vol. 109, No. 4 ( 2018-04), p. 1101-1109
Abstract:
Cancer stem cells ( CSC s) are thought to play important roles in cancer malignancy. Previously, we successfully induced sphere cancer stem‐like cells ( CSLC s) from several cell lines and observed the property of chemoresistance. In the present study, we examined the metastatic potential of these induced CSLC s. Sphere cancer stem‐like cells were induced from a human hepatoma cell line ( SK ‐ HEP ‐1) in a unique medium containing neural survival factor‐1. Splenic injection of cells into immune‐deficient mice was used to assess hematogenous liver metastasis. Transcriptomic strand‐specific RNA ‐sequencing analysis, quantitative real‐time PCR , and flow cytometry were carried out to examine the expression of epithelial‐mesenchymal transition ( EMT )‐related genes. Splenic injection of CSLC s resulted in a significantly increased frequency of liver metastasis compared to parental cancer cells ( P 〈 .05). In CSLC s, a mesenchymal marker, Vimentin, and EMT ‐promoting transcription factors, Snail and Twist1, were upregulated compared to parental cells. Correspondingly, significant enrichment of the molecular signature of the EMT in CSLC s relative to parental cancer cells was shown ( q 〈 0.01) by RNA ‐sequencing analysis. This analysis also revealed differential expression of CD 44 isoforms between CSLC s and parental cancer cells. Increasing CD 44 isoforms containing an extra exon were observed, and the standard CD 44 isoform decreased in CSLC s compared to parental cells. Interestingly, another CD 44 variant isoform encoding a short cytoplasmic tail was also upregulated in CSLC s (11.7‐fold). Our induced CSLC s possess an increased liver metastatic potential in which promotion of the EMT and upregulation of CD 44 variant isoforms, especially short‐tail, were observed.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2018.109.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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