Department of Oral Oncology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
Center of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, Japan.
Anticancer Res. 2023 Nov;43(11):4833-4841. doi: 10.21873/anticanres.16680.
BACKGROUND/AIM: The interaction of integrin αvβ8 with type I collagen was shown to promote oral squamous cell carcinoma (SCC) cell proliferation via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. However, the role of integrin αvβ8 in SCC progression remains poorly understood. In this study, the role of integrin αvβ8 in oral SCC progression was therefore investigated.
Integrin αv and β8 protein expression in oral SCC cells was examined by western blotting. Oral SCC cell motility was investigated using modified Boyden chamber assays. Behavior of oral SCC cells was examined in three-dimensional culture using type I collagen gel. Ras homolog family member A (RHOA), Ras-related C3 botulinum toxin substrate 1 (RAC1), and cell division control protein 42 homolog (CDC42) activity of oral SCC cells was analyzed by pull-down assays.
SCC cells with high integrin αvβ8 expression levels had a high ability to migrate on type I collagen and exhibited enhanced invasion into type I collagen gel. In SCC cells with high integrin αvβ8 expression level, cultivation on type I collagen induced RAC1 activation. Treatment with RAC1 inhibitor reduced type I collagen-induced motility of SCC cells. Down-regulation of integrin β8 by specific antisense oligonucleotide reduced type I collagen-induced RAC1 activation and suppressed cell motility and invasion into type I collagen gel.
The interaction of integrin αvβ8 with type I collagen facilitates SCC cell motility and invasion via RAC1 activation. Therefore, integrin αvβ8 and RAC1 may represent new targets for inhibiting metastasis and invasion in patients with oral SCC.
背景/目的：已有研究表明，整合素αvβ8 与 I 型胶原的相互作用通过丝裂原活化蛋白激酶/细胞外信号调节激酶通路促进口腔鳞状细胞癌（SCC）细胞增殖。然而，整合素αvβ8 在 SCC 进展中的作用仍知之甚少。因此，本研究旨在探讨整合素αvβ8 在口腔 SCC 进展中的作用。
通过 Western blot 检测口腔 SCC 细胞中整合素αv 和β8 蛋白的表达。通过改良 Boyden 室测定法研究口腔 SCC 细胞的迁移能力。使用 I 型胶原凝胶在三维培养中研究口腔 SCC 细胞的行为。通过下拉测定法分析口腔 SCC 细胞中 Ras 同源家族成员 A（RHOA）、Ras 相关 C3 肉毒杆菌毒素底物 1（RAC1）和细胞分裂控制蛋白 42 同源物（CDC42）的活性。
高表达整合素αvβ8 的 SCC 细胞在 I 型胶原上具有很强的迁移能力，并表现出增强的侵袭 I 型胶原凝胶的能力。在高表达整合素αvβ8 的 SCC 细胞中，在 I 型胶原上培养诱导 RAC1 激活。RAC1 抑制剂处理降低了 I 型胶原诱导的 SCC 细胞迁移。特异性反义寡核苷酸下调整合素β8 降低了 I 型胶原诱导的 RAC1 激活，并抑制了细胞在 I 型胶原凝胶中的迁移和侵袭。
整合素αvβ8 与 I 型胶原的相互作用通过 RAC1 激活促进 SCC 细胞的迁移和侵袭。因此，整合素αvβ8 和 RAC1 可能成为抑制口腔 SCC 患者转移和侵袭的新靶点。
