Abstract

Hepatocellular carcinoma (HCC) is a primary liver cancer that usually develops in the setting of chronic inflammation and liver damage. The hepatic microenvironment plays a crucial role in the disease development, as players such as hepatic stellate cells, resident liver macrophages (Kupffer cells), endothelial cells, extracellular matrix, and a variety of immune cells interact in highly complex and intertwined signaling pathways. A key factor in these cross-talks are platelets, whose role in cancer has gained growing evidence in recent years. Platelets have been reported to promote HCC cell proliferation and invasion, but their involvement goes beyond the direct effect on tumor cells, as they are known to play a role in pro-fibrinogenic signaling and the hepatic immune response, as well as in mediating interactions between these factors in the stroma. Anti-platelet therapy has been shown to ameliorate liver injury and improve the disease outcome. However, platelets have also been shown to play a crucial role in liver regeneration after organ damage. Therefore, the timing and microenvironmental setting need to be kept in mind when assessing the potential effect and therapeutic value of platelets in the disease progression, while further studies are needed for understanding the role of platelets in patients with HCC.

Highlights

  • Hepatocellular carcinoma (HCC) is a primary liver cancer that usually develops in the setting of chronic liver damage

  • This environment includes hepatic stellate cells (HSC), resident liver macrophages (Kupffer cells), endothelial cells, extracellular matrix (ECM), a variety of immune cells, as well as newly-formed, leaky and dysfunctional blood vessels that typically occur in cirrhosis and HCC [3,4,5]

  • Hepatocellular carcinoma is an inflammatory-related cancer that usually occurs in the context of hepatic injury and inflammation

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Summary

Introduction

Hepatocellular carcinoma (HCC) is a primary liver cancer that usually develops in the setting of chronic liver damage. Hepatocellular carcinoma initiation and progression are set in a background of chronic inflammation, which creates a micro-environment favorable for tumor growth [2] This environment includes hepatic stellate cells (HSC), resident liver macrophages (Kupffer cells), endothelial cells, extracellular matrix (ECM), a variety of immune cells, as well as newly-formed, leaky and dysfunctional blood vessels that typically occur in cirrhosis and HCC [3,4,5]. Besides a potential direct effect on HCC cells, platelets interact with different cell types in the stroma, including hepatic stellate cells, endothelial cells, and hepatic immune cells [12,13] (Figure 1). We provide an overview on the role of platelets in the pathogenesis of HCC, both by focusing on the direct effect on tumor cells and their role in the tumor microenvironment (Figure 1)

The Effect of Platelets on HCC Proliferation and Metastasis
The Role of Platelets in HSC Activation
Platelets and the Hepatic Immune Response
Thrombocytosis and Thrombocytopenia in Liver Disease
Targeting
Findings
Conclusions
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