Co-Expression of CD34, CD90, OV-6 and Cell-Surface Vimentin Defines Cancer Stem Cells of Hepatoblastoma, Which Are Affected by Hsp90 Inhibitor 17-AAG.

Mieun Lee-Theilen,Delaine D Fadini,Julia Eichhorn,Giulietta Volante,Henning C Fiegel,Julia R Hadhoud,Udo Rolle

doi:10.3390/cells10102598

Mieun Lee-Theilen, Delaine D Fadini + Show 5 more

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https://doi.org/10.3390/cells10102598

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Journal: Cells	Publication Date: Sep 29, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: University Hospital Frankfurt, Goethe University Frankfurt

Abstract

Cancer stem cells (CSCs) are nowadays one of the major focuses in tumor research since this subpopulation was revealed to be a great obstacle for successful treatment. The identification of CSCs in pediatric solid tumors harbors major challenges because of the immature character of these tumors. Here, we present CD34, CD90, OV-6 and cell-surface vimentin (csVimentin) as reliable markers to identify CSCs in hepatoblastoma cell lines. We were able to identify CSC characteristics for the subset of CD34+CD90+OV-6+csVimentin+-co-expressing cells, such as pluripotency, self-renewal, increased expression of EMT markers and migration. Treatment with Cisplatin as the standard chemotherapeutic drug in hepatoblastoma therapy further revealed the chemo-resistance of this subset, which is a main characteristic of CSCs. When we treated the cells with the Hsp90 inhibitor 17-AAG, we observed a significant reduction in the CSC subset. With our study, we identified CSCs of hepatoblastoma using CD34, CD90, OV-6 and csVimentin. This set of markers could be helpful to estimate the success of novel therapeutic approaches, as resistant CSCs are responsible for tumor relapses.

Highlights

Hepatoblastoma is the most common pediatric liver tumor and is usually diagnosed within the first 5 years of life [1]
Cancer Stem Cell Markers CD34, CD90, OV-6 and Cell-Surface Vimentin Were Co-Expressed on a Subset of Hepatoblastoma Cells
In order to define a set of markers for the identification of Cancer stem cells (CSCs) in hepatoblastoma, we analyzed the expression of CD133, CXCR4, CD34 and CD90 in the hepatoblastoma cell lines HepG2 and HuH6 using flow cytometry

Summary

Introduction

Hepatoblastoma is the most common pediatric liver tumor and is usually diagnosed within the first 5 years of life [1]. The International Pediatric Liver Consensus Classification subdivides the tumors by histology in fetal, embryonal, cholangioblastic, macrotrabecular and small-cell undifferentiated (SCUD) patterns. These tumors are of high heterogeneity with often closely intermixed histological components [2,3,4]. CSCs are a minor fraction of cancer cells and, like normal stem cells, possess the ability to self-renew, and provide multiple mature progenies [6] This fraction of the tumor cells was found to be highly tumorigenic and responsible for drug resistance, metastasis and high relapse rates in certain cancers [6].

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