Department of Oral and Maxillofacial Surgery and Oral Pathology, Amsterdam UMC-Location, VUMC/Academic Centre for Dentistry Amsterdam (ACTA), PO Box 7057, 1007, Amsterdam, The Netherlands.
Amsterdam UMC-Location VUmc, Otolaryngology-Head and Neck Surgery, Cancer Center, Amsterdam, The Netherlands.
J Cancer Res Clin Oncol. 2023 Jul;149(8):4173-4184. doi: 10.1007/s00432-022-04307-4. Epub 2022 Sep 2.
c-Met, a receptor tyrosine kinase, is involved in the growth, invasion and metastasis of a variety of cancers. In a set of cell lines from several solid tumors, a five-fold increase in c-Met expression after irradiation has been reported. This study aimed to assess if c-Met is likewise abundantly expressed in oral tongue squamous cell carcinoma (OTSCC) upon exposure to irradiation, followed by a Met-induced biological response.
Six OTSCC cell lines were exposed to gamma radiation doses of 2, 4, and 6 Gray. The changes in c-Met protein levels were assessed by western blot and flow cytometry. c-Met gene expression, cell migration, proliferation and cell cycle assays were performed as phenotypic readouts.
Irradiation resulted in upregulation of c.Met in all cell lines with different time kinetics. On average the cells displayed minimal c-Met expression on their surface ranging from 5 to 30% of total protein. Abrupt downregulation of c-Met surface expression occurred one hour after radiation but recovered 48 h post-radiation. Intracellularly, the highest level of expression was found on day 5 after radiation exposure. Irradiation induced aggressive invasive potential of the cells as determined in cell migration assays, particularly in cell lines with the highest c-Met expression.
These results provide novel insights into both intracellular and extracellular dynamics of c-Met expression profiles upon irradiation of OTSCC cells in vitro. It might also suggest that radiation enhances cell migration, indicative of invasiveness, through c-Met up-regulation, at least for certain types of OTSCC cells.
c-Met 是一种受体酪氨酸激酶，参与多种癌症的生长、侵袭和转移。在一组来自几种实体瘤的细胞系中，已经报道照射后 c-Met 的表达增加了五倍。本研究旨在评估 c-Met 在暴露于照射后是否同样在口腔舌鳞状细胞癌 (OTSCC) 中大量表达，随后发生 Met 诱导的生物学反应。
将 6 种 OTSCC 细胞系暴露于 2、4 和 6 Gray 的 γ 射线剂量下。通过 Western blot 和流式细胞术评估 c-Met 蛋白水平的变化。进行 c-Met 基因表达、细胞迁移、增殖和细胞周期测定作为表型读出。
照射导致所有细胞系的 c.Met 上调，具有不同的时程动力学。平均而言，细胞表面的 c-Met 表达最低，总蛋白的 5%至 30%。辐射后 1 小时表面 c-Met 表达急剧下调，但辐射后 48 小时恢复。细胞内，在辐射暴露后第 5 天发现表达水平最高。细胞迁移测定表明，照射诱导细胞侵袭潜力增加，尤其是在 c-Met 表达最高的细胞系中。
这些结果为体外照射 OTSCC 细胞时 c-Met 表达谱的细胞内和细胞外动态提供了新的见解。它还可能表明，辐射通过 c-Met 上调增强了细胞迁移，提示侵袭性，至少对于某些类型的 OTSCC 细胞是如此。
