Aquino Iara Gonçalves, Cuadra-Zelaya Florence Juana Maria, Bizeli Ana Laura Valença, Palma Patricia Vianna Bonini, Mariano Fernanda Viviane, Salo Tuula, Coletta Ricardo Della, Bastos Débora Campanella, Graner Edgard
Departamento de Diagnóstico Oral, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas (UNICAMP), Piracicaba, São Paulo, Brazil.
Department of Pathology, School of Dentistry, University of El Salvador, San Salvador, El Salvador.
Oral Dis. 2024 Nov;30(8):4886-4897. doi: 10.1111/odi.15003. Epub 2024 May 20.
To isolate cancer stem cells (CSC) from a metastatic oral squamous cell carcinoma (OSCC) cell line and investigate their in vitro and in vivo phenotypic characteristics.
Subpopulations with individual staining intensities for CD44 and CD326 were isolated from the OSCC cell line LN-1A by FACS: CD44/CD326 (CSC-M), CD44/CD326 (CSC-E), and CD44/CD326 (CSC-M). Proliferation, clonogenic potential, adhesion, migration, epithelial-mesenchymal transition markers, and sensitivity to cisplatin and TVB-3166 were analyzed in vitro. Tumor formation and metastasis were assessed by subcutaneous and orthotopic inoculations into BALB/c mice.
E-cadherin levels were higher in CSC-E cells while vimentin and Slug more produced by CSC-M cells. CSC-M and CSC-M subpopulations showed higher proliferation, produced more colonies, and have stronger adhesion to the extracellular matrix. All cell lines established tumors; however, CSC-E and CSC-M formed larger masses and produced more metastases.
The CSC subpopulations here described show increased cancer capabilities in vitro, tumorigenic and metastatic potential in vivo, and may be exploited in the search for novel therapeutic targets for OSCC.
从转移性口腔鳞状细胞癌（OSCC）细胞系中分离癌症干细胞（CSC），并研究其体外和体内表型特征。
通过荧光激活细胞分选术（FACS）从OSCC细胞系LN-1A中分离出具有不同CD44和CD326染色强度的亚群：CD44⁺/CD326⁺（CSC-M）、CD44⁻/CD326⁺（CSC-E）和CD44⁺/CD326⁻（CSC-L）。对其增殖、克隆形成能力、黏附、迁移、上皮-间质转化标志物以及对顺铂和TVB-3166的敏感性进行体外分析。通过皮下和原位接种到BALB/c小鼠中评估肿瘤形成和转移情况。
CSC-E细胞中E-钙黏蛋白水平较高，而CSC-M细胞中波形蛋白和Slug的产生更多。CSC-M和CSC-L亚群显示出更高的增殖能力，形成更多的集落，并且对细胞外基质具有更强的黏附力。所有细胞系均形成肿瘤；然而，CSC-E和CSC-M形成更大的肿块并产生更多转移灶。
本文描述的CSC亚群在体外显示出增强的癌症能力，在体内具有致瘤和转移潜力，可能有助于寻找OSCC的新型治疗靶点。
