Optimization of tissue processing for immunohistochemistry for the detection of human glypican-3

Takai, Haruki; Kato, Atsuhiko; Ishiguro, Takahiro; Kinoshita, Yasuko; Karasawa, Yayoi; Otani, Yoshimi; Sugimoto, Masamichi; Suzuki, Masami; Kataoka, Hiroaki

doi:10.1016/j.acthis.2008.11.025

Cited by 22 publications

(28 citation statements)

References 29 publications

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“…Shirakawa and colleagues previously found that almost half of the HCC cases showed the mixed pattern (cytoplasm and membrane) and the other half showed only the cytoplasmic pattern 31. A recent study was performed using HepG2 xenograft tissues to optimize the tissue processing method for GPC3 immunohistochemistry 52. Further studies are needed to clarify whether a different localization of GPC3 has a different functional significance and a diagnostic value.…”

Section: Gpc3 Immunohistochemistry For Hcc Tumor Diagnosismentioning

confidence: 99%

Glypican-3: A new target for cancer immunotherapy

Kim

2011

European Journal of Cancer

194

189

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Hepatocellular carcinoma (HCC) remains a common malignant cancer worldwide. There is an urgent need to identify new molecular targets for the development of novel therapeutic approaches. Here, we review the structure, function and biology of Glypican-3 (GPC3) and its role in human cancer with a focus on its potential as a therapeutic target for immunotherapy. GPC3 is a cell-surface protein that is over-expressed in HCC. Loss-of-function mutations of GPC3 cause Simpson-Golabi-Behmel syndrome, a rare X-linked overgrowth condition. GPC3 binds Wnt and Hedgehog signaling proteins. GPC3 is also able to bind basic growth factors such as fibroblast growth factor 2 through its heparan sulfate glycan chains. GPC3 is a promising candidate for liver cancer therapy given that it shows high expression in HCC. An anti-GPC3 monoclonal antibody has shown anti-cancer activity in mice and its humanized IgG molecule is currently undergoing clinical evaluation in patients with HCC. There is also evidence that soluble GPC3 may be a useful serum biomarker for HCC.

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Section: Gpc3 Immunohistochemistry For Hcc Tumor Diagnosismentioning

confidence: 99%

Glypican-3: A new target for cancer immunotherapy

Kim

2011

European Journal of Cancer

194

189

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“…At the end of the in-life stage, the xenograft mice were sacrificed using the same method as for Experiment 1 and the spleens were 10 5 molecules per cell), 26 was obtained from ATCC and cultured in Eagle's minimum essential medium (Sigma-Aldrich Japan) supplemented with 10% (v/v) FBS, 0.1 mM non-essential amino acids and 1.0 mM sodium pyruvate.…”

Section: Methodsmentioning

confidence: 99%

“…As for the GPC3 function relevant to macrophages, we have reported that macrophage infiltration is stimulated by GPC3 membranous expression in human clinical HCC as well removed and fixed and embedded in paraffin using the PLP-AMeX method. [26][27][28][29] Histopathological evaluation. Thin sections from the paraffin specimens were prepared and stained with HE to evaluate morphological changes.…”

Section: Methodsmentioning

confidence: 99%

Histopathological analyses of the antitumor activity of anti-glypican-3 antibody (GC33) in human liver cancer xenograft models: The essential role of macrophages

Takai¹,

Kato²,

Kinoshita³

et al. 2009

Cancer Biology & Therapy

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Previously, we demonstrated the antitumor efficacy of the antiglypican-3 (GPC3) antibody GC33 in several human liver cancer xenograft models and the important role of antibody-dependent cellular cytotoxicity (ADCC) in the antitumor mechanism of GC33. Involvement of other mechanisms such as modulation of the functions of GPC3 in antitumor activity remains to be elucidated. In this study, we investigated histopathologically time-course changes in xenografts in mice following a single administration of GC33 to clarify the morphological changes contributing to the tumor growth inhibition of GC33, including the changes in GPC3-related factors/components [proliferation, extracelluar matrices (ECMs) and macrophage]. Histopathological changes peaked 3-5 d after GC33 administration and included increased tumor cell death, tumor cells with round morphology, multinucleated tumor cells and small spindle/round-like cells (mostly F4/80-positive macrophages). No direct effects of GC33 on proliferation activity of tumor cells were observed. Meanwhile, alteration of ECM structures and a remarkable increase in macrophages was noted in the GC33-treated group. Increase in macrophages was observed mainly in the outer layer of tumor nodules; the area of the increase approximately included the area where the change in tumor cells and ECMs were observed. Interestingly, depletion of macrophages in the xenograft models resulted in a marked reduction of the antitumor activity of GC33. In the in vitro ADCC assay, ADCC was only slightly induced by mouse peritoneal macrophages. These data suggest that macrophages play an important role in the antitumor activity of GC33, which is not likely to be direct ADCC by macrophages themselves.

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“…Because of its specific expression in HCC cells, cell surface GPC3 may serve as a promising therapeutic target for HCC. GC33 is a recently developed mouse monoclonal antibody raised against the C‐terminal ectodomain region (amino acid positions between 524 and 563) of human GPC3 (13, 14). Notably, GC33 showed significant antitumour activity mediated by antibody‐dependent cellular cytotoxicity in vivo (13, 14).…”

mentioning

confidence: 99%