Experimental Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Cancer Sci. 2022 Sep;113(9):3244-3254. doi: 10.1111/cas.15359. Epub 2022 May 18.
Laryngeal squamous cell carcinoma (LSCC), although one of the most common head and neck cancers, has a static or slightly decreased survival rate because of difficulties in early diagnosis, lack of effective molecular targeting therapy, and severe dysfunction after radical surgical treatments. Therefore, a novel therapeutic target is crucial to increase treatment efficacy and survival rates in these patients. Glycoprotein NMB (GPNMB), whose role in LSCC remains elusive, is a type 1 transmembrane protein involved in malignant progression of various cancers, and its high expression is thought to be a poor prognostic factor. In this study, we showed that GPNMB expression levels in LSCC samples are significantly higher than those in normal tissues, and GPNMB expression is observed mostly in growth-arrested cancer cells. Furthermore, knockdown of GPNMB reduces monolayer cellular proliferation, cellular migration, and tumorigenic growth, while GPNMB protein displays an inverse relationship with Ki-67 levels. Therefore, we conclude that GPNMB may be an attractive target for future LSCC therapy.
喉鳞状细胞癌(LSCC)是最常见的头颈部癌症之一,但由于早期诊断困难、缺乏有效的分子靶向治疗以及根治性手术后严重功能障碍,其生存率保持不变或略有下降。因此,对于这些患者,寻找新的治疗靶点对于提高治疗效果和生存率至关重要。糖蛋白 NMB(GPNMB)在 LSCC 中的作用仍不清楚,它是一种 1 型跨膜蛋白,参与多种癌症的恶性进展,其高表达被认为是预后不良的因素。在本研究中,我们表明 LSCC 样本中的 GPNMB 表达水平明显高于正常组织,并且 GPNMB 表达主要观察到在生长停滞的癌细胞中。此外,敲低 GPNMB 可降低单层细胞增殖、细胞迁移和致瘤性生长,而 GPNMB 蛋白与 Ki-67 水平呈负相关。因此,我们得出结论,GPNMB 可能是未来 LSCC 治疗的一个有吸引力的靶点。