Mechanisms involved in breast cancer liver metastasis

Abstract

Liver metastasis is a frequent occurrence in patients with breast cancer; however, the available treatments are limited and ineffective. While liver-specific homing of breast cancer cells is an important feature of metastasis, the formation of liver metastases is not random. Indeed, breast cancer cell factors contribute to the liver microenvironment. Major breakthroughs have been achieved recently in understanding breast cancer liver metastasis (BCLM). The process of liver metastasis consists of multiple steps and involves various factors from breast cancer cells and the liver microenvironment. A further understanding of the roles of breast cancer cells and the liver microenvironment is crucial to guide future work in clinical treatments. In this review we discuss the contribution of breast cancer cells and the liver microenvironment to liver metastasis, with the aim to improve therapeutic efficacy for patients with BCLM.

Figure 1

A model for breast cancer liver metastasis. (i) intravasation: invasive breast cancer cell invades through the endothelium of a tumor blood vessel into circulation; (ii) circulation: breast cancer cell survives in the blood vessels without any attachment; (iii) margination: circulating breast cancer cell arrests at the site of liver by adhering to the sinusoidal endothelial cell via specific sets of adhesion molecules; (iv) extravasation: the migrated breast cancer cell invades through the endothelial wall of sinusoidal endothelial cell, migrates and finally proliferates in the liver; and (v) colonization: breast cancer cells survive and form a life-threatening focus in liver.