Serglycin’s role in primary liver cancer: insights into tumor microenvironment and macrophage interaction

作者：Qinghai Lian, Chao Ma, Xiaoxiao Wang, Jiani Wang, Jindi Zeng, Jiongshan Zhang, Yongwei Li · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1668627 · 被引用次数：9 · 研究领域：Proteoglycans and glycosaminoglycans research、Immune cells in cancer、Liver physiology and pathology

Background Serglycin (SRGN) is an important proteoglycan that regulates tumorigenesis, but its role in primary liver cancer (PLC) remains unclear. Methods We investigated the expression and prognostic potential of SRGN in PLC using bioinformatics analyses. HepG2 cells were transfected with an SRGN over expression vector and their proliferation, migration, invasion, resistance to sorafenib, and angiogenic capacity were examined in vitro . A subcutaneous xenograft tumor model was created using nude mice. SRGN overexpressing hepatoma cells were co-cultured with THP-1 derived macrophages. The expressions of CD80 and CD206, secretory molecules, and the NF-κB and STAT3 signal pathways were examined by flow cytometry, ELISA and western blot, respectively. Transwell migration and invasion were investigated in HepG2 and Huh7 co-cultured with SRGN-promoted macrophages. Results Single-cell analysis revealed SRGN expression across 17 distinct cell subpopulations, with higher expression in macrophages in tumor tissues compared to those in normal tissues. SRGN displayed consistent high expression across cell cycle phases while exhibited dynamic expression during macrophage pseudotime trajectory. Cell communication analysis indicated that SRGN was involved in interactions within the tumor microenvironment (TME), particularly in the VEGF signaling network. Autocrine SRGN promoted in vitro aggressiveness, especially pro-angiogenic activity, and in vivo tumorigenicity of HepG2 cells, and confe...