The expression profile of glypican-3 and its relation to macrophage population in human hepatocellular carcinoma

Background: Glypican-3 (GPC3) is frequently upregulated in hepatocellular carcinoma (HCC). Analysis of GPC3-deficient mice implies GPC3 involvement in macrophage-lineage cells.

Aim: In this study, we first assessed the association of GPC3 expression with the macrophage population in liver tissues from 30 HCC patients using immunohistochemistry.

Methods: The GPC3 expression was categorized into three patterns – one with GPC3-negative staining and two with GPC3-positive staining (one with unclear membrane staining and one with clear membrane staining, designated GPC3+/C). The number of macrophages that were stained with resident macrophage (rMϕ) or pan-macrophage (pMϕ) markers was counted for each GPC3 expression pattern.

Results: GPC3 immunoreactivity was observed in 76.7% of the HCC specimens. No significant differences were observed in the number of rMϕ marker-positive cells among the three expression patterns. In contrast, the GPC3+/C pattern showed a significantly higher number of pMϕ-positive cells compared with the other two patterns, most of which tended to take on the morphology of migrating macrophages. A second experiment conducted to compare macrophage infiltration between the xenograft tissues of a GPC3-transfected HCC cell line and its parent GPC3-nonexpressing cell line revealed that the increase in macrophages was stimulated by membrane expression of GPC3.

Conclusion: The observations suggest that the increased macrophages in the GPC3+/C pattern are likely to be recruited macrophages, not resident macrophages, and that the expression of GPC3 in the membrane is involved in macrophage recruitment.