Araki-Maeda Hanako, Kawabe Mutsuki, Omori Yuji, Yamanegi Koji, Yoshida Kazunari, Yoshikawa Kyohei, Takaoka Kazuki, Noguchi Kazuma, Nakano Yoshiro, Kishimoto Hiromitsu
Department of Oral and Maxillofacial Surgery, Hyogo Medical University, Nishinomiya, Japan.
Department of Pathology, Hyogo Medical University, Nishinomiya, Japan.
J Dent Sci. 2022 Oct;17(4):1471-1479. doi: 10.1016/j.jds.2022.04.018. Epub 2022 May 21.
BACKGROUND/PURPOSE: Vascular endothelial growth factor receptor (VEGFR) expression in oral squamous cell carcinoma (OSCC) promotes tumor growth through both autocrine and paracrine signaling. VEGF-positive OSCC cases are associated with a high depth of invasion, increased metastasis, and poor prognosis. In this study we established and then molecularly and functionally analyzed an OSCC cell line that co-expresses VEGF-A, VEGFR-1, and VEGFR-2, termed HCM-SqCC010 cells.
VEGF-A, VEGFR-1, and VEGFR-2 expression in HCM-SqCC010 cells were examined by immunohistochemistry and immunoblotting. Expression and inhibition of VEGF-A, VEGFR-1, and VEGFR-2 in HCM-SqCC010 cells were verified by quantitative real-time PCR.
Our analysis of HCM-SqCC010 cells revealed that their proliferation depended on VEGF-A, and selective inhibition of VEGFR-1 or VEGFR-2 resulted in decreased cell growth.
We established an OSCC cell line, HCM-SqCC010, that expresses VEGF-A, VEGFR-1, and VEGFR-2. This triple-positive cell line showed no effect from a molecular targeted drug toward VEGF-A, but it did show strong cell growth inhibition in response to a VEGFR inhibitor. Thus, new therapeutic strategies against OSCC should include a VEGFR inhibitor.
背景/目的:口腔鳞状细胞癌(OSCC)中血管内皮生长因子受体(VEGFR)的表达通过自分泌和旁分泌信号促进肿瘤生长。VEGF阳性的OSCC病例与高侵袭深度、转移增加和预后不良相关。在本研究中,我们建立了一种共表达VEGF-A、VEGFR-1和VEGFR-2的OSCC细胞系,命名为HCM-SqCC010细胞,并对其进行了分子和功能分析。
通过免疫组织化学和免疫印迹检测HCM-SqCC010细胞中VEGF-A、VEGFR-1和VEGFR-2的表达。通过定量实时PCR验证HCM-SqCC010细胞中VEGF-A、VEGFR-1和VEGFR-2的表达及抑制情况。
我们对HCM-SqCC010细胞的分析表明,它们的增殖依赖于VEGF-A,选择性抑制VEGFR-1或VEGFR-2会导致细胞生长减少。
我们建立了一种表达VEGF-A、VEGFR-1和VEGFR-2的OSCC细胞系HCM-SqCC010。这种三阳性细胞系对针对VEGF-A的分子靶向药物无反应,但对VEGFR抑制剂有强烈的细胞生长抑制作用。因此,针对OSCC的新治疗策略应包括VEGFR抑制剂。