Taniguchi Gentaro, Kajino Kazunori, Momose Shuji, Saeki Harumi, Yue Liang, Ohtsuji Naomi, Abe Masaaki, Shibuya Tomoyoshi, Orimo Akira, Nagahara Akihito, Watanabe Sumio, Hino Okio
Department of Molecular Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Department of Gastroenterology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Cancers (Basel). 2022 Apr 28;14(9):2198. doi: 10.3390/cancers14092198.
The expression of Renal Carcinoma (ERC)/mesothelin is enhanced in a variety of cancers. ERC/mesothelin contributes to cancer progression by modulating cell signals that regulate proliferation and apoptosis. Based on such biological insights, ERC/mesothelin has become a molecular target for the treatment of mesothelioma, pancreatic cancer, and ovarian cancer. Recent studies revealed about 50-60% of colorectal adenocarcinomas also express ERC/mesothelin. Therefore, colorectal cancer can also be a potential target of the treatment using an anti-ERC/mesothelin antibody. We previously demonstrated an anti-tumor effect of anti-ERC antibody 22A31 against mesothelioma. In this study, we investigated the effect of 22A31 on a colorectal adenocarcinoma cell line, HCT116. The cells were xenografted into BALB/c nu/nu mice. All mice were randomly allocated to either an antibody treatment group with 22A31 or isotype-matched control IgG1κ. We compared the volume of subsequent tumors, and tumors were pathologically assessed by immunohistochemistry. Tumors treated with 22A31 were significantly smaller than those treated with IgG1κ and contained significantly fewer mitotic cells with Ki67 staining. We demonstrated that 22A31 exhibited a growth inhibitory property on HCT116. Our results implied that ERC/mesothelin-targeted therapy might be a promising treatment for colorectal cancer.
肾癌（ERC）/间皮素在多种癌症中表达增强。ERC/间皮素通过调节调控增殖和凋亡的细胞信号促进癌症进展。基于这些生物学见解，ERC/间皮素已成为治疗间皮瘤、胰腺癌和卵巢癌的分子靶点。最近的研究显示，约50%-60%的结直肠癌腺癌也表达ERC/间皮素。因此，结直肠癌也可能是使用抗ERC/间皮素抗体进行治疗的潜在靶点。我们之前证明了抗ERC抗体22A31对间皮瘤具有抗肿瘤作用。在本研究中，我们调查了22A31对结直肠腺癌细胞系HCT116的作用。将这些细胞接种到BALB/c nu/nu小鼠体内。所有小鼠被随机分配到接受22A31抗体治疗的组或同型匹配的对照IgG1κ组。我们比较了后续肿瘤的体积，并通过免疫组织化学对肿瘤进行病理评估。用22A31治疗的肿瘤明显小于用IgG1κ治疗的肿瘤，并且Ki67染色显示有丝分裂细胞明显更少。我们证明了22A31对HCT116具有生长抑制特性。我们的结果表明，针对ERC/间皮素的疗法可能是结直肠癌一种有前景的治疗方法。
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