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.


OBJECTIVE
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 (rMvarphi) or pan-macrophage (pMvarphi) 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 rMvarphi marker-positive cells among the three expression patterns. In contrast, the GPC3+/C pattern showed a significantly higher number of pMvarphi-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.


CONCLUSIONS
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.
Takai
Hirotake
H
Safety Assessment Department, Chugai Pharmaceutical Co. Ltd, Shizuoka, Japan. takaihrt@chugai-pharm.co.jp
Kato
Atsuhiko
A
Kato
Chie
C
Watanabe
Takeshi
T
Matsubara
Koichi
K
Suzuki
Masami
M
Kataoka
Hiroaki
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D005260:Female; D053673:Glypicans / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D055806:Microvessels / Q000276:immunology; D008875:Middle Aged; D014162:Transfection
D018952:Antigens, CD34; D000943:Antigens, Differentiation; C105937:GPC3 protein, human; D053673:Glypicans; C036763:monocyte-macrophage differentiation antigen; D003094:Collagen