Monoclonal Antibody Targeting of the Cell Surface Molecule TM4SF5 Inhibits the Growth of Hepatocellular Carcinoma

Kwon, Sang-Hoon; Choi, Kyung-Chan; Kim, Young Eun; Ha, Yang-Wha; Kim, Dongbum; Wu, Guang; Kim, Doo-Sik; Lee, Younghee; Kwon, Hyung‐Joo

doi:10.1158/0008-5472.can-13-2730

Cited by 19 publications

(43 citation statements)

References 33 publications

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“…We previously showed that the anti-TM4SF5 antibody induced changes in actin polymerization and formation of focal adhesion sites in HCC cells based on phalloidin and paxillin staining [42]. However, we found that there was no change in colon cancer cells (data not shown).…”

Section: Resultsmentioning

confidence: 55%

“…Previously, we found that treatment of HCC cells expressing TM4SF5 with anti-TM4SF5 antibody enhances expression of E-cadherin [42]. We therefore checked expression of E-cadherin using confocal microscopy and Western blotting analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Using this technology, we showed that TM4SF5 can serve as a molecular target for HCC and colon cancer: a peptide vaccine targeting TM4SF5 had preventive or therapeutic effects against HCC and colon cancer in mouse models [38-41]. Therefore, we postulated that TM4SF5-specific monoclonal antibody can serve as a therapeutic antibody to treat these cancers and we recently proved that injection of anti-TM4SF5 antibody can suppress the growth of HCC tumor in a mouse model [42]. …”

Section: Introductionmentioning

confidence: 99%

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Therapeutic effect of a TM4SF5-specific monoclonal antibody against colon cancer in a mouse model

Kim

Kwon

et al. 2014

Oncotarget

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Transmembrane 4 superfamily member 5 protein (TM4SF5) is presumed to serve as a molecular target to prevent or treat hepatocellular carcinoma (HCC) and colon cancer in a mouse model. Previously, we reported the efficacy of anti-cancer peptide vaccine targeting TM4SF5. In addition, we reported an anti-proliferative effect of anti-TM4SF5 monoclonal antibody in HCC. Here, we investigated expression of TM4SF5 in 45 primary colon cancer tissues. Almost all of the colon cancer tissues expressed TM4SF5 based on immunohistochemistry using anti-TM4SF5 monoclonal antibody. The treatment of human colon cancer cells with anti-TM4SF5 antibody reduced growth of TM4SF5 expressing cells and enhanced expression of E-cadherin and β-catenin. Using mouse colon cancer models, we then evaluated the in vivo anti-cancer effect of anti-TM4SF5 antibody. Injection of the antibody significantly reduced growth of tumors priorly established by subcutaneous injection of human colon cancer cells HT-29 in a xenograft setting. We obtained similar results with mouse colon cancer cell line CT-26 in an allograft setting. Therefore, we suggest that the TM4SF5-specific monoclonal antibody has a therapeutic effect against colon cancer.

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Section: Resultsmentioning

confidence: 55%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Therapeutic effect of a TM4SF5-specific monoclonal antibody against colon cancer in a mouse model

Kim

Kwon

et al. 2014

Oncotarget

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“…It was passaged for less than 6 months after receipt and used in spiking experiments of the current study. The cell line was characterized by the cell bank based on cell morphology, post-freeze viability, isoenzyme analysis, DNA fingerprinting analysis, mycoplasma contamination test, and bacterial and fungal contamination (33). The cell line was maintained in DMEM (Gibco) supplemented with 10% FBS…”

Section: Cell Linementioning

confidence: 99%

Clinical Significance of EpCAM mRNA-Positive Circulating Tumor Cells in Hepatocellular Carcinoma by an Optimized Negative Enrichment and qRT-PCR–Based Platform

Guo

Yang

Sun

et al. 2014

Clinical Cancer Research

107

117

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Purpose: This study aimed to construct a novel platform for the detection of circulating tumor cells (CTC) in patients with hepatocellular carcinoma (HCC) and to investigate the clinical significance of epithelial cell adhesion molecule mRNA-positive (EpCAM mRNAþ ) CTCs using this platform.Experimental Design: An optimized platform for CTC detection was constructed by evaluating different negative enrichment, mRNA isolation, and cDNA synthesis procedures and compared with the CellSearch system. A total of 299 patients with HCC were recruited into this prospective study; of these, 157 who received curative resection, 76 who received transcatheter arterial chemoembolization (TACE), and 66 who received radiotherapy were tested using our platform. The diagnostic value of EpCAM mRNAþ CTCs was investigated in 122 patients with HCC who underwent resection and 120 control subjects.Results: The optimized negative enrichment and quantitative real-time PCR (qRT-PCR)-based CTC detection platform had high sensitivity, specificity, and reproducibility and a low sample volume requirement. This platform showed a potential diagnostic value in patients with HCC and exhibited 76.7% consistency with the CellSearch system (r ¼ 0.54, P < 0.050). Pretreatment CTC level showed prognostic significance in patients with HCC treated with resection, TACE, and radiotherapy (all P < 0.050). Most of the patients showed a decrease in CTC levels after treatment that reflected tumor response. In contrast, patients with an increased CTC level showed disease progression after treatment.Conclusions: We established an optimized platform based on negative enrichment and qRT-PCR for highly sensitive, specific, and reproducible CTC detection. This platform might be clinically useful in auxiliary diagnosis, treatment response assessment, and early decision-making to tailor the most effective antitumor strategies. Clin Cancer Res; 20(18); 4794-805. Ó2014 AACR.

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“…We found TM4SF5, which was over-expressed in gastric cance r (Tab. 2), which was also over-expressed in other kinds of cancer (23)(24)(25)(26), so drew the CNC network between TM4SF5 and LncRNAs by PCC (Fig. 4a).…”

Section: Construction Of the Coding-non-coding Gene Co-expression Netmentioning

confidence: 99%

TM4SF5-CTD-2354A18.1-miR-4697-3P may play a key role in the pathogenesis of gastric cancer

Df¹,

Mf²,

Sl³

et al. 2015

BLL

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Monoclonal Antibody Targeting of the Cell Surface Molecule TM4SF5 Inhibits the Growth of Hepatocellular Carcinoma

Cited by 19 publications

References 33 publications

Therapeutic effect of a TM4SF5-specific monoclonal antibody against colon cancer in a mouse model

Therapeutic effect of a TM4SF5-specific monoclonal antibody against colon cancer in a mouse model

Clinical Significance of EpCAM mRNA-Positive Circulating Tumor Cells in Hepatocellular Carcinoma by an Optimized Negative Enrichment and qRT-PCR–Based Platform

TM4SF5-CTD-2354A18.1-miR-4697-3P may play a key role in the pathogenesis of gastric cancer

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