Cela Ilaria, Caponio Vito Carlo Alberto, Capone Emily, Pinti Morena, Mascitti Marco, Togni Lucrezia, Lo Muzio Lorenzo, Rubini Corrado, De Laurenzi Vincenzo, Lattanzio Rossano, Perrotti Vittoria, Sala Gianluca
Department of Innovative Technologies in Medicine & Dentistry, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Oral Dis. 2024 May;30(4):2039-2050. doi: 10.1111/odi.14719. Epub 2023 Aug 31.
The aim of the present study was to evaluate the expression of intracellular and vesicular LGALS3BP in oral squamous cell carcinoma (OSCC) patients and available cell lines to explore its potential as a target for antibody-drug conjugate (ADC) therapy.
Free and vesicular LGALS3BP expression levels were evaluated in cancer tissues from a cohort of OSCC patients as well as in a panel of OSCC cell lines through immunohistochemistry, qRT-PCR, Western Blot analysis, and ELISA.
LGALS3BP resulted in being highly expressed in the cytoplasm of tumour cells in OSCC patient tissues. A strong correlation was found between high LGALS3BP expression levels and aggressive histological features of OSCC. Biochemistry analysis performed on OSCC cell lines showed that LGALS3BP is expressed in all the tested cell lines and highly enriched in cancer-derived extracellular vesicles. Moreover, LGALS3BP high-expressing HOC621 and CAL27 OSCC cell lines showed high sensitivity to the ADC-payload DM4, with an IC around 0.3 nM.
The present study highlights that LGALS3BP is highly expressed in OSCC suggesting a role as a potential diagnostic biomarker and therapeutic target for ADC-based therapy.
本研究旨在评估细胞内和囊泡型LGALS3BP在口腔鳞状细胞癌(OSCC)患者及现有细胞系中的表达,以探索其作为抗体药物偶联物(ADC)治疗靶点的潜力。
通过免疫组织化学、qRT-PCR、蛋白质免疫印迹分析和酶联免疫吸附测定(ELISA),评估一组OSCC患者癌组织以及一组OSCC细胞系中游离型和囊泡型LGALS3BP的表达水平。
LGALS3BP在OSCC患者组织的肿瘤细胞胞质中高表达。LGALS3BP高表达水平与OSCC侵袭性组织学特征之间存在强相关性。对OSCC细胞系进行的生物化学分析表明,LGALS3BP在所有测试细胞系中均有表达,且在癌症来源的细胞外囊泡中高度富集。此外,高表达LGALS3BP的HOC621和CAL27 OSCC细胞系对ADC有效载荷DM4表现出高敏感性,半数抑制浓度(IC)约为0.3 nM。
本研究强调LGALS3BP在OSCC中高表达,提示其作为基于ADC治疗的潜在诊断生物标志物和治疗靶点的作用。