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

IF 3.5 3区 医学 Q1 DERMATOLOGY
Keiko Tanegashima, Yuka Tanaka, Takamichi Ito, Yoshinao Oda, Takeshi Nakahara
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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.

Abstract Image

皮肤鳞状细胞癌中 TROP2 的表达及其治疗意义:免疫组化和功能分析的启示
皮肤鳞状细胞癌(cSCC)是一种常见的皮肤癌,但对晚期病例的治疗效果有限。滋养层细胞表面抗原2(TROP2)是一种细胞表面蛋白,在各种肿瘤中广泛表达,对肿瘤细胞的生长、凋亡、迁移、侵袭和转移等关键过程有重要影响。萨妥珠单抗-戈维替康(Sacituzumab govitecan)是一种靶向TROP2的抗体-药物共轭物(ADC),正在成为一种前景广阔的抗癌治疗策略。在这项研究中,我们调查了 51 名患者的 cSCC 组织中 TROP2 的表达情况,并评估了它在 A431 人类 SCC 细胞系中的功能。免疫组化分析显示 TROP2 在 cSCC 组织和 A431 细胞的质膜上表达。A431细胞对sacituzumab govitecan表现出敏感性,存活细胞数显著减少,且呈浓度依赖性。此外,敲除TROP2会导致细胞周期蛋白D1和BCL-2的表达减少,同时降低细胞活力。敲除 TROP2 还会导致波形蛋白表达减少,同时降低迁移能力。这些研究结果表明,TROP2 在 cSCC 细胞增殖和迁移中起着至关重要的作用,并凸显了沙西妥珠单抗戈维替康作为一种治疗 cSCC 的药物的潜力。
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来源期刊
Experimental Dermatology
Experimental Dermatology 医学-皮肤病学
CiteScore
6.70
自引率
5.60%
发文量
201
审稿时长
2 months
期刊介绍: Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.
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