Graduate School of Dentistry (Second Department of Oral and Maxillofacial Surgery), Osaka Dental University, Hirakata 573-1121, Japan.
Department of Advanced Molecular Therapy, Graduate School of Medicine, Faculty of Medicine, Osaka University, Suita 565-0871, Japan.
Cells. 2024 Aug 13;13(16):1341. doi: 10.3390/cells13161341.
Tongue squamous cell carcinoma (TSCC) occurs frequently in the oral cavity, and because of its high proliferative and metastatic potential, it is necessary to develop a novel treatment for it. We have reported the importance of the inhibition of the periostin (POSTN) pathological splicing variant, including exon 21 (PN1-2), in various malignancies, but its influence is unclear in tongue cancer. In this study, we investigated the potential of POSTN exon 21-specific neutralizing antibody (PN21-Ab) as a novel treatment for TSCC. Human was transfected into the human TSCC (HSC-3) and cultured under stress, and PN2 was found to increase cell viability. PN2 induced chemotherapy resistance in HSC-3 via the phosphorylation of the cell survival signal Akt. In tissues from human TSCC and primary tumors of an HSC-3 xenograft model, PN1-2 was expressed in the tumor stroma, mainly from fibroblasts. The intensity of mRNA expression was positively correlated with malignancy. In the HSC-3 xenograft model, CDDP and PN21-Ab promoted CDPP's inhibition of tumor growth. These results suggest that POSTN exon 21 may be a biomarker for tongue cancer and that PN21-Ab may be a novel treatment for chemotherapy-resistant tongue cancer. The treatment points towards important innovations for TSCC, but many more studies are needed to extrapolate the results.
舌鳞状细胞癌（TSCC）常发生于口腔，由于其具有高增殖和转移潜能，因此有必要开发新的治疗方法。我们已经报道了抑制骨膜蛋白（POSTN）病理性剪接变异体，包括外显子 21（PN1-2）在各种恶性肿瘤中的重要性，但在舌癌中的影响尚不清楚。在本研究中，我们研究了 POSTN 外显子 21 特异性中和抗体（PN21-Ab）作为治疗 TSCC 的新方法的潜力。将 转染到人类 TSCC（HSC-3）中并在应激下培养，发现 PN2 增加了细胞活力。PN2 通过细胞存活信号 Akt 的磷酸化诱导 HSC-3 产生化疗耐药性。在人类 TSCC 组织和 HSC-3 异种移植模型的原发性肿瘤中，PN1-2 表达于肿瘤基质中，主要来自成纤维细胞。mRNA 表达强度与恶性程度呈正相关。在 HSC-3 异种移植模型中，CDDP 和 PN21-Ab 促进了 CDDP 对肿瘤生长的抑制作用。这些结果表明 POSTN 外显子 21 可能是舌癌的生物标志物，PN21-Ab 可能是治疗化疗耐药性舌癌的新方法。该治疗方法为 TSCC 带来了重要的创新，但需要更多的研究来推断结果。
