Activated Human Hepatic Stellate Cells Promote Growth of Human Hepatocellular Carcinoma in a Subcutaneous Xenograft Nude Mouse Model

Abstract

Tumor cell microenvironment defines cancer development, also in hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs) are believed to be the key contributors to tumor microenvironment in HCC, yet their precise role in cancer progression is still unclear. The aim of this study was to determine the effect of human HSCs on progression of HCC using a subcutaneous xenograft nude mouse model. Nude mice were stratified to receive subcutaneous injections of human HCC cell line HepG2 and human HSC line LX-2 (HepG2 + LX-2), HepG2 alone, LX-2 alone, or phosphate-buffered saline. Tumor growth was assessed by measuring tumor size. After 30 days, final tumor size, weight, and histology were assessed. Compared with mice that were only injected HepG2 cells, mice injected with HepG2 + LX-2 exhibited more rapid tumor growth, increased tumor size and weight, higher tumor cell numbers due to increased proliferation and reduced apoptosis, increased fibrotic bands containing LX-2 cells, and increased tumor angiogenesis. In conclusion, HSCs play a significant role in promotion of HCC growth.