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

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY BMB Reports Pub Date : 2024-02-05 DOI:10.5483/BMBRep.2023-0228
Soyeon Lim, Youngeun Ha, Boram Lee, Junho Shin, Taiyoun Rhim
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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.
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作为双重角色生物标记物的钙粘连蛋白:肺癌的抗体诊断和靶向治疗
肺癌是死亡率最高的癌症之一。与其他恶性肿瘤相比,肺癌通常在晚期才被诊断出来,而且治疗方案有限。本研究重点关注作为肺癌诊断和治疗潜在生物标志物的钙连蛋白。Calnexin是一种与N-连接糖蛋白合成密不可分的分子伴侣蛋白,它与癌症有一些关联。然而,利用钙连蛋白进行靶向治疗或诊断的方法尚未被提出。我们通过 1D-LCMSMS 鉴定了作为肺癌生物标志物的 calnexin,并利用 Western 印迹、流式细胞术和免疫细胞化学证实了它在人类肺癌细胞膜中的表达。抗卡络蛋白抗体对肺癌细胞系具有补体依赖性细胞毒性,从而显著降低了皮下异种移植模型中的肿瘤生长。此外,我们还验证了使用钙粘蛋白抗体通过体内成像标记肿瘤的可行性。此外,钙连蛋白的外泌体检测表明,液体活检在诊断方面具有潜在的实用性。总之,这项研究确立了钙粘蛋白作为基于抗体的肺癌诊断和治疗靶点的前景,为早期检测和治疗开辟了新的途径。
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来源期刊
BMB Reports
BMB Reports 生物-生化与分子生物学
CiteScore
5.10
自引率
7.90%
发文量
141
审稿时长
1 months
期刊介绍: The BMB Reports (BMB Rep, established in 1968) is published at the end of every month by Korean Society for Biochemistry and Molecular Biology. Copyright is reserved by the Society. The journal publishes short articles and mini reviews. We expect that the BMB Reports will deliver the new scientific findings and knowledge to our readers in fast and timely manner.
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