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钙连蛋白作为一种双重作用的生物标志物:肺癌的抗体诊断和治疗靶点。

Calnexin as a dual-role biomarker: antibody-based diagnosis and therapeutic targeting in lung cancer.

机构信息

Department of Bioengineering, College of Engineering, Hanyang University, Seoul 04763, Korea.

出版信息

BMB Rep. 2024 Mar;57(3):155-160. doi: 10.5483/BMBRep.2023-0228.

Abstract

Lung cancer carries one of the highest mortality rates among all cancers. It is often diagnosed at more advanced stages with limited treatment options compared to other malignancies. This study focuses on calnexin as a potential biomarker for diagnosis and treatment of lung cancer. Calnexin, a molecular chaperone integral to N-linked glycoprotein synthesis, has shown some associations with cancer. However, targeted therapeutic or diagnostic methods using calnexin have been proposed. Through 1D-LCMSMS, we identified calnexin as a biomarker for lung cancer and substantiated its expression in human lung cancer cell membranes using Western blotting, flow cytometry, and immunocytochemistry. Anti-calnexin antibodies exhibited complement-dependent cytotoxicity to lung cancer cell lines, resulting in a notable reduction in tumor growth in a subcutaneous xenograft model. Additionally, we verified the feasibility of labeling tumors through in vivo imaging using antibodies against calnexin. Furthermore, exosomal detection of calnexin suggested the potential utility of liquid biopsy for diagnostic purposes. In conclusion, this study establishes calnexin as a promising target for antibody-based lung cancer diagnosis and therapy, unlocking novel avenues for early detection and treatment. [BMB Reports 2024; 57(3): 155-160].

摘要

肺癌是所有癌症中死亡率最高的一种。与其他恶性肿瘤相比,肺癌通常在晚期诊断,治疗选择有限。本研究专注于钙连蛋白作为诊断和治疗肺癌的潜在生物标志物。钙连蛋白是一种与 N-连接糖蛋白合成有关的分子伴侣,与癌症有一定的关联。然而,尚未提出使用钙连蛋白的靶向治疗或诊断方法。通过 1D-LCMSMS,我们鉴定出钙连蛋白是肺癌的生物标志物,并通过 Western blot、流式细胞术和免疫细胞化学证实其在人肺癌细胞膜中的表达。抗钙连蛋白抗体对肺癌细胞系表现出补体依赖性细胞毒性,导致皮下移植瘤模型中的肿瘤生长显著减少。此外,我们通过针对钙连蛋白的抗体在体内成像验证了标记肿瘤的可行性。此外,外泌体检测钙连蛋白提示液体活检在诊断方面具有潜在的应用价值。总之,本研究确立了钙连蛋白作为基于抗体的肺癌诊断和治疗的有前途的靶标,为早期检测和治疗开辟了新途径。[BMB Reports 2024; 57(3): 155-160]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/733c/10979343/679195b245fc/bmb-57-3-155-f1.jpg

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