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TROP2 表达与皮肤鳞状细胞癌的治疗意义:免疫组化和功能分析的见解。

TROP2 Expression and Therapeutic Implications in Cutaneous Squamous Cell Carcinoma: Insights From Immunohistochemical and Functional Analysis.

机构信息

Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Exp Dermatol. 2024 Oct;33(10):e15196. doi: 10.1111/exd.15196.

Abstract

Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer, but treatments for advanced cases have limited efficacy. Trophoblast cell-surface antigen 2 (TROP2) is a cell-surface protein that is widely expressed in various tumours, where it exerts significant influence over critical processes such as tumour cell growth, apoptosis, migration, invasion and metastasis. Sacituzumab govitecan, an antibody-drug conjugate (ADC) targeting TROP2, is emerging as a promising strategy for anticancer therapy. In this study, we investigated TROP2 expression in cSCC tissues from 51 patients and evaluated its function in the A431 human SCC cell line. Immunohistochemical analysis revealed TROP2 expression on the plasma membrane of cSCC tissues and A431 cells. A431 cells showed sensitivity to sacituzumab govitecan with a significant concentration-dependent decrease in viable cell number. In addition, Knockdown of TROP2 resulted in decreased expression of cyclin D1 and BCL-2, along with reduced cell viability. Knockdown of TROP2 also resulted in decreased expression of vimentin, along with reduced migratory capacity. These findings suggest that TROP2 plays a crucial role in cSCC cell proliferation and migration, and highlight the potential of sacituzumab govitecan as a promising therapeutic option for cSCC.

摘要

皮肤鳞状细胞癌(cSCC)是一种常见的皮肤癌,但晚期病例的治疗方法疗效有限。滋养细胞表面抗原 2(TROP2)是一种广泛表达于各种肿瘤的细胞表面蛋白,它对肿瘤细胞生长、凋亡、迁移、侵袭和转移等关键过程有重要影响。针对 TROP2 的抗体药物偶联物(ADC)——戈沙妥珠单抗,正成为一种有前途的抗癌治疗策略。在本研究中,我们检测了 51 例 cSCC 组织中 TROP2 的表达情况,并评估了其在 A431 人 SCC 细胞系中的功能。免疫组织化学分析显示 TROP2 在 cSCC 组织和 A431 细胞的质膜上表达。A431 细胞对戈沙妥珠单抗敏感,活细胞数随浓度依赖性显著减少。此外,TROP2 敲低导致 cyclin D1 和 BCL-2 表达减少,细胞活力降低。TROP2 敲低还导致波形蛋白表达减少,迁移能力降低。这些发现表明 TROP2 在 cSCC 细胞增殖和迁移中起关键作用,并强调了戈沙妥珠单抗作为 cSCC 有前途的治疗选择的潜力。

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