In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 262-262
Abstract:
Cancer stem cells (CSCs) are considered a pivotal target for the eradication of liver cancer. CSCs have been identified by the use of various stem cell markers; however, it remains unclear how individual CSC markers are expressed in individual tumors. We hypothesized that the distinct marker-positive CSCs show unique features of tumorigenicity/metastasis and chemosensitivity which may reflect the heterogeneous nature of hepatocellular carcinoma (HCC). Gene expression profiling and immunohistochemistry analyses were used to analyze 364 tumor specimens. Fluorescence-activated cell sorting (FACS) was used to isolate marker-positive HCC cells, which were tested for hepatic stem/progenitor cell properties. CSC markers EpCAM and CD90 are independently expressed in primary liver cancer. EpCAM+ cells share features with tumorigenic epithelial stem cells, whereas CD90+ cells share those of metastatic vascular endothelial cells with expression of c-Kit. CD90+ cells facilitate metastasis of EpCAM+ cells through activation of TGF-beta signaling, and this effect is abolished by c-Kit inhibitor imatinib mesylate. These distinct tumorigenic/metastatic CSCs can evolve from marker-negative cells de novo, and their frequencies vary dramatically according to the genomic alterations and genotoxic stress. Our results suggest that liver CSCs are not a single, static entity but rather exist heterogeneously and undergo dynamic changes through genomic alteration and genotoxic stress. The evolution of CSCs explains the enrichment of CSCs in advanced cancer and the limitation of targeting marker-positive CSCs alone for tumor eradication. Citation Format: Taro Yamashita, Masao Honda, Kouki Nio, Yasumasa Hara, Takehiro Hayashi, Naoki Oishi, Hajime Sunakozaka, Hajime Takatori, Shuichi Kaneko. The evolution of diverse cancer stem cells in human liver cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 262. doi:10.1158/1538-7445.AM2013-262
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-262
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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