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探讨阶段特异性胚胎抗原 3 在口腔癌进展中的作用及其作为紫杉烷类化疗潜在靶点的可能性。

Exploring stage‑specific embryonic antigen 3 involvement in oral cancer progression and as a potential target for taxane‑based chemotherapy.

机构信息

Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, University of The Ryukyus, Nishihara, Okinawa 903‑0215, Japan.

Department of Otorhinolaryngology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903‑0215, Japan.

出版信息

Oncol Rep. 2023 Oct;50(4). doi: 10.3892/or.2023.8619. Epub 2023 Aug 24.

Abstract

Despite significant advancements in therapeutic approaches, oral neoplasms remain formidable and life‑threatening conditions that affect a substantial number of individuals worldwide. Within oral malignancies, a subset of cancer stem cells (CSCs) represent a crucial population responsible for tumor initiation and progression. The identification of reliable markers for the detection and characterization of CSCs in solid tumors, particularly in the context of oral cancers, remains an ongoing challenge. Stage‑specific embryonic antigen 3 (SSEA3), previously associated with mesenchymal stem cells and linked to the progression of breast neoplasms and poor prognosis, has yet to be comprehensively elucidated in the context of oral malignancies. The present study aimed to investigate the expression and properties of SSEA3 in 16 distinct subsets of human oral neoplastic cell lines, classified as either CD44 positive (+) or CD44 negative (‑). For the first time, SSEA3 was examined as an indicator of tumorigenicity and resistance to taxane‑derived chemotherapeutic agents. In the majority of oral neoplastic cell lines analyzed, SSEA3 was expressed in a small population of CD44(+) cells. Significantly, SSEA3(+) cells exhibited heightened proliferative activity and upregulated expression of genes associated with stem cells compared with SSEA3(‑) cells. The aforementioned findings suggested that SSEA3 may contribute to the evolution and progression of oral malignancies by fostering tumor growth. Furthermore, SSEA3(+) cells displayed increased sensitivity to taxane‑based pharmaceuticals, indicating the potential for SSEA3 to be a viable target in the treatment schema for oral cavity neoplasms. In conclusion, the present study provides novel insight into the role of SSEA3 in the progression and management of oral neoplasms, potentially paving the way for more effective therapeutic approaches.

摘要

尽管治疗方法取得了重大进展,但口腔肿瘤仍然是严重威胁生命的疾病,影响着全球大量人群。在口腔恶性肿瘤中,癌症干细胞 (CSC) 是一个重要的亚群,负责肿瘤的起始和进展。在实体瘤中,包括口腔癌在内,寻找可靠的标志物来检测和鉴定 CSC 仍然是一个持续的挑战。阶段特异性胚胎抗原 3 (SSEA3) 先前与间充质干细胞有关,与乳腺癌肿瘤的发生和不良预后有关,但在口腔恶性肿瘤中的作用尚未得到全面阐明。本研究旨在研究 SSEA3 在 16 种不同的人类口腔肿瘤细胞系中的表达和特性,这些细胞系分为 CD44 阳性 (+) 或 CD44 阴性 (‑)。首次将 SSEA3 作为肿瘤发生和对紫杉烷类化疗药物耐药性的指标进行了研究。在分析的大多数口腔肿瘤细胞系中,SSEA3 在一小部分 CD44(+) 细胞中表达。重要的是,与 SSEA3(‑) 细胞相比,SSEA3(+) 细胞具有更高的增殖活性和与干细胞相关基因的上调表达。上述发现表明,SSEA3 可能通过促进肿瘤生长来促进口腔恶性肿瘤的演进和进展。此外,SSEA3(+) 细胞对紫杉烷类药物表现出更高的敏感性,表明 SSEA3 可能成为口腔腔隙肿瘤治疗方案中的一个可行靶点。总之,本研究为 SSEA3 在口腔肿瘤进展和管理中的作用提供了新的见解,可能为更有效的治疗方法铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2b/10485803/73aef99dfed7/or-50-04-08619-g00.jpg

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