Abstract

Transendothelial migration is a pivotal step before the dissemination of tumor cells into the blood circulation. Related researches about the crosstalk between tumor cells and endothelial cells could contribute to understanding the mechanism of transendothelial migration. Cumulative studies showed that CD133 was an important marker for cancer stem cells. In our research, a co-culture system was developed to study the interaction between CD133+ liver cancer cells and human umbilical vein endothelial cells. The results showed that the direct co-cultured supernatants promoted the migration and invasion of CD133+ liver cancer cells. It was further investigated that the expression level of chemokine CXCL9 was significantly elevated in the culture supernatants of direct co-culture system by activating the NF-kB, rather than in the indirect co-culture system or mono-culture system. High expression of CXCL9 in the direct co-cultured supernatants played a significant role in enhancing the migration and invasion of CD133+ liver cancer cells. Collectively, these findings suggest that chemokine CXCL9 may function as a potential target during the process of transendothelial migration.

Highlights

  • Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancerassociated deaths, which is over 600,000 around the world [1]

  • The supernatants in the direct co-culture system of human umbilical vein endothelial cells (HUVEC) and CD133+ liver cancer cells promoted the metastatic properties of CD133+ liver cancer cells

  • In order to investigate the interaction between HUVEC and the CD133+ liver cancer cells, both the indirect and direct co-culture systems were used

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancerassociated deaths, which is over 600,000 around the world [1]. The development of a metastatic trait is rather complex, but the process generally consists of the following phases: primary cancer cell migration and invasion, transendothelial migration (TEM) into the circulation, extravasation, and distant seeding [3]. Liver cancer stem cells (CSCs) are postulated as a small subset of undifferentiated cells in liver cancer. They mirror the characteristics of embryonic or pluripotent stem cells, and they are responsible for liver cancer relapse and chemoresistance [4, 5]. CD133 cell surface glycoprotein has been reported as an important marker for liver cancer stem cells and is used for the identification and isolation of CSCs from liver cancer tissues as well as cell lines [6, 7]

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