Experimental dermatology · 2024
TROP2 Expression and Therapeutic Implications in Cutaneous Squamous Cell Carcinoma: Insights From Immunohistochemical and Functional Analysis.
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Tanegashima Keiko, Tanaka Yuka, Ito Takamichi, Oda Yoshinao, Nakahara Takeshi
Аннотация
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.
Предметные рубрики MeSH
HumansSkin NeoplasmsCarcinoma, Squamous CellAntigens, NeoplasmCell Adhesion MoleculesCell Line, TumorAntibodies, Monoclonal, HumanizedCell MovementCell SurvivalImmunohistochemistryImmunoconjugatesFemaleGene Knockdown TechniquesCyclin D1VimentinProto-Oncogene Proteins c-bcl-2AgedCell ProliferationMiddle AgedMaleApoptosisCamptothecin