Journal Article

NPC1 promotes the progression of hepatocellular carcinoma by mediating the accumulation of neutrophils into the tumor microenvironment

Yang, Songhai, Chen, Jiangming, Liu, Fubao, Xie, Kun

2025

Overview

Hepatocellular carcinoma remains a significant threat to human health. Recent studies have found that the intake of cellular cholesterol contributes to the development and progression of hepatocellular carcinoma, although the exact mechanisms remain unclear. Our analysis of transcriptomic and proteomic databases has identified increased mRNA and protein expression levels of NPC1, a cholesterol intracellular transporter protein, in hepatocellular carcinoma tissues. This increase is significantly associated with a worse prognosis for patients. To corroborate these findings, we performed immunohistochemical staining of NPC1 on liver tissue samples from patients, revealing significantly higher expression levels of NPC1 in hepatocellular carcinoma tissues compared to normal tissues. Subsequent investigations have revealed that NPC1 expression does not significantly influence the proliferation of hepatocellular carcinoma cells in vitro. However, it has a substantial inhibitory effect on the progression of hepatocellular carcinoma tumors when observed in vivo. Utilizing flow cytometry to monitor cellular changes within the tumor microenvironment has led us to discover that NPC1 plays a crucial role in the regulation of neutrophil recruitment within the tumor. Using further neutrophil depletion experiments, we determined that the role of NPC1 in advancing hepatocellular carcinoma progression truly relies on neutrophils. These observations are further reinforced by a comprehensive analysis of clinical databases alongside immunohistochemistry findings. In conclusion, our research suggests that NPC1's overexpression could contribute to hepatocellular carcinoma progression by promoting neutrophil recruitment, positioning NPC1 as a promising new biomarker and therapeutic target for hepatocellular carcinoma. Compared to normal tissues, NPC1 expression is significantly elevated in hepatocellular carcinoma tissues. Our findings indicate that NPC1 plays a key role in regulating neutrophil recruitment within the tumor, which is a critical factor in the progression of hepatocellular carcinoma and is closely linked to poor patient outcomes. Overall, our results suggest that NPC1 promotes tumor progression by facilitating neutrophil accumulation.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Animals / biomarkers / Biomarkers, Tumor - metabolism / Cancer Genetics and Genomics / Cancer therapies / Carbon dioxide / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - metabolism / Carcinoma, Hepatocellular - pathology / Cell Line, Tumor / Cell Proliferation / Cells / Chemotherapy / Cholesterol / Cloning / Disease Progression / Esophagus / Female / Flow cytometry / Gene expression / Hepatitis / Hepatocellular carcinoma / hepatoma / human health / Humans / Immunohistochemistry / Kinases / Laboratory animals / Leukocytes (neutrophilic) / liver / Liver Cancer / Liver cirrhosis / Liver Neoplasms - genetics / Liver Neoplasms - metabolism / Liver Neoplasms - pathology / Male / Medical prognosis / Metabolism / Mice / Neutrophils / Neutrophils - metabolism / NPC1 / Npc1 protein / Patients / prognosis / protein synthesis / Protein transport / Proteins / Proteomics / Radiation therapy / Sterols / the tumor microenvironment / Therapeutic targets / therapeutics / Transcriptomics / transport proteins / Tumor Microenvironment / Tumors