In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5336-5336
Abstract:
Recent evidences suggest that a certain type of hepatocellular carcinoma (HCC) is hierarchically organized by a subset of cells with stem cell features (cancer stem cells: CSCs). Although CSCs have been identified using several CSC markers and are now considered a pivotal target for the eradication of HCC, little information is known about the characteristics of marker-positive cells. Here we explored the expression of CSC markers CD90 and EpCAM in primary HCCs and cell lines to investigate the molecular characteristics of each cell type. Gene expression profiling and immunohistochemistry analyses were used to characterize 340 surgically resected HCC tissues and 11 advanced HCC tissues with distant organ metastasis obtained from autopsy. Magnetic-activated cell sorting was used to isolate EpCAM+ or CD90+ cells from surgically resected 12 fresh HCC specimens, which were tested for hepatic stem cell properties including their tumor initiating capacity in NOD/SCID mice. In primary HCC, EpCAM+ and CD90+ cells resided distinctively, and gene expression analysis of sorted cells suggested that EpCAM+ cells had the features of epithelial stem cells whereas CD90+ cells had those of vascular endothelial cells. Clinicopathological analysis indicated that presence of EpCAM+ cells was associated with poorly differentiated morphology and high serum AFP with a tendency of portal vein invasion, while the presence of CD90+ cells was associated with high incidence of distant organ metastasis within two years after surgical resection and advanced TNM stages. Serial xenotransplantation of EpCAM+/CD90+ cells in NOD/SCID mice revealed the rapid growth of EpCAM+ cells in the subcutaneous lesion and highly metastatic capacity of CD90+ cells into the lung. Xenotransplantation experiments of cell lines further demonstrated that EpCAM+ cells had the features of hepatic CSCs with marked tumorigenic capacity whereas CD90+ cells had those of vascular endothelial cells with highly metastatic features. Markedly, CD90+ cells showed the abundant expression of c-Kit and VEGFR1 and chemosensitivity to imatinib methylate (c-Kit inhibitor) and axitinib (VEGFR1/2 inhibitor). Taken together, our data strongly suggest the discrete natures of EpCAM+ and CD90+ cells with specific gene expression patterns and chemosensitivity to the molecularly targeted therapy. The presence of distinct CSCs may determine the clinical outcome of HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5336. doi:1538-7445.AM2012-5336
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-5336
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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