Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma

Hara, Hisashi; Takahashi, Tsuyoshi; Serada, Satoshi; Fujimoto, Minoru; Ohkawara, Tomoharu; Nakatsuka, Rie; Harada, Emi; Nishigaki, Takahiko; Takahashi, Yusuke; Nojima, Satoshi; Miyazaki, Yasuhiro; Makino, Tomoki; Kurokawa, Yukinori; Yamasaki, Makoto; Miyata, Hiroshi; Nakajima, Kiyokazu; Takiguchi, Shuji; Morii, Eiichi; Mori, Masaki; Doki, Yuichiro; Naka, Tetsuji

doi:10.1038/bjc.2016.183

Cited by 85 publications

(103 citation statements)

References 35 publications

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“…[12][13][14] Recently, our group identified glypican-1 (GPC1) as a cancer antigen in esophageal squamous cell carcinoma (ESCC) by a quantitative proteomic approach focused on cell surface membrane proteins. 15 We confirmed the limited or relatively low expression of GPC1 in normal tissues compared with ESCC tissues. 16 GPC1 is a heparan sulfate proteoglycan that binds to the external surface of the plasma membrane by a glycosyl-phosphatidylinositol anchor.…”

supporting

confidence: 74%

“…Recently, our group identified glypican‐1 (GPC1) as a cancer antigen in esophageal squamous cell carcinoma (ESCC) by a quantitative proteomic approach focused on cell surface membrane proteins . We confirmed the limited or relatively low expression of GPC1 in normal tissues compared with ESCC tissues .…”

mentioning

confidence: 52%

“…Curves were fitted according to nonlinear regression analysis of the data using GraphPad Prism v6.0 software. Results are reported as IC 50 , the concentration of compound needed to yield a 50% reduction in viability compared with vehicle‐treated cells (control = 100%) as described previously …”

Section: Methodsmentioning

confidence: 99%

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Anti‐glypican‐1 antibody‐drug conjugate exhibits potent preclinical antitumor activity against glypican‐1 positive uterine cervical cancer

Matsuzaki

Serada

Hiramatsu

et al. 2017

Intl Journal of Cancer

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Glypican-1 (GPC1) is highly expressed in solid tumors, especially squamous cell carcinomas (SCCs), and is thought to be associated with disease progression. We explored the use of a GPC1-targeted antibody-drug conjugate (ADC) as a novel treatment for uterine cervical cancer. On immunohistochemical staining, high expression levels of GPC1 were detected in about 50% of uterine cervical cancer tissues and also in a tumor that had relapsed after chemoradiotherapy. Novel anti-GPC1 monoclonal antibodies were developed, and clone 01a033 was selected as the best antibody for targeted delivery of the cytotoxic agent monomethyl auristatin F (MMAF) into GPC1-positive cells. The anti-GPC1 antibody was conjugated with MMAF. On flow cytometry, HeLa and ME180 cervical cancer cells highly expressed GPC1, however, RMG-I ovarian clear cell cancer cell line showed weak expression. The GPC1-ADC was rapidly internalized into GPC1-expressing cells in vitro and was potently cytotoxic to cancer cells highly expressing GPC1. There were no inhibitory effects on cancer cells with low expression of GPC1. In a murine xenograft model, GPC1-ADC also had significant and potent tumor growth inhibition. GPC1-ADC-mediated G2/M phase cell cycle arrest was detected, indicating that the dominant antitumor effect in vivo was MMAF-mediated. The toxicity of GPC-ADC was tolerable within the therapeutic dose range in mice. Our data showed that GPC1-ADC has potential as a promising therapy for uterine cervical cancer.

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confidence: 74%

mentioning

confidence: 52%

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Anti‐glypican‐1 antibody‐drug conjugate exhibits potent preclinical antitumor activity against glypican‐1 positive uterine cervical cancer

Matsuzaki

Serada

Hiramatsu

et al. 2017

Intl Journal of Cancer

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“…In human diseases, GPC1 exosomes have been investigated as a specific biomarker for the early diagnosis of pancreatic cancer in recent years . Other GPC1‐related diseases include breast cancer, esophageal squamous cell carcinoma, ameloblastoma, prostate cancer, neuroendocrine tumors, etc. The association between GPC2 and human diseases has not been clarified to date.…”

Section: Structure and Expression Of Glypicansmentioning

confidence: 99%

Glypican‐3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment

Zhou

Shang

et al. 2017

Medicinal Research Reviews

274

192

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Liver cancer is the second leading cause of cancer-related deaths, and hepatocellular carcinoma (HCC) is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican-3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis. Mechanistic studies have revealed that GPC3 functions in HCC progression by binding to molecules such as Wnt signaling proteins and growth factors. Moreover, GPC3 has been used as a target for molecular imaging and therapeutic intervention in HCC. To date, GPC3-targeted magnetic resonance imaging, positron emission tomography, and near-infrared imaging have been investigated for early HCC detection, and various immunotherapeutic protocols targeting GPC3 have been developed, including the use of humanized anti-GPC3 cytotoxic antibodies, treatment with peptide/DNA vaccines, immunotoxin therapies, and genetic therapies. In this review, we summarize the current knowledge regarding the structure, function, and biology of GPC3 with a focus on its clinical potential as a diagnostic molecule and a therapeutic target in HCC immunotherapy.

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“…There has been evidence that GPC3 expression or other glypicans (e.g., GPC1) has been correlated with poor prognosis in hepatocellular carcinoma or other types of cancer (30)(31)(32)(33). To analyze a possible correlation between GPC2 mRNA levels and survival of patients with neuroblastoma, we used the R2 Genomics Analysis and Visualization Platform.…”

Section: Gpc2 Is Highly Expressed In Neuroblastoma But Not In Normal mentioning

confidence: 99%

Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma

Hewitt

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

111

126

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Neuroblastoma is a childhood cancer that is fatal in almost half of patients despite intense multimodality treatment. This cancer is derived from neuroendocrine tissue located in the sympathetic nervous system. Glypican-2 (GPC2) is a cell surface heparan sulfate proteoglycan that is important for neuronal cell adhesion and neurite outgrowth. In this study, we find that GPC2 protein is highly expressed in about half of neuroblastoma cases and that high GPC2 expression correlates with poor overall survival compared with patients with low GPC2 expression. We demonstrate that silencing of GPC2 by CRISPR-Cas9 or siRNA results in the inhibition of neuroblastoma tumor cell growth. GPC2 silencing inactivates Wnt/ β-catenin signaling and reduces the expression of the target gene N-Myc, an oncogenic driver of neuroblastoma tumorigenesis. We have isolated human single-domain antibodies specific for GPC2 by phage display technology and found that the single-domain antibodies can inhibit active β-catenin signaling by disrupting the interaction of GPC2 and Wnt3a. To explore GPC2 as a potential target in neuroblastoma, we have developed two forms of antibody therapeutics, immunotoxins and chimeric antigen receptor (CAR) T cells. Immunotoxin treatment was demonstrated to inhibit neuroblastoma growth in mice. CAR T cells targeting GPC2 eliminated tumors in a disseminated neuroblastoma mouse model where tumor metastasis had spread to multiple clinically relevant sites, including spine, skull, legs, and pelvis. This study suggests GPC2 as a promising therapeutic target in neuroblastoma.glypican | neuroblastoma | single-domain antibody | chimeric antigen receptor T-cell therapy | immunotoxin

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Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma

Cited by 85 publications

References 35 publications

Anti‐glypican‐1 antibody‐drug conjugate exhibits potent preclinical antitumor activity against glypican‐1 positive uterine cervical cancer

Anti‐glypican‐1 antibody‐drug conjugate exhibits potent preclinical antitumor activity against glypican‐1 positive uterine cervical cancer

Glypican‐3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment

Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma

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