Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, South Korea.
NGeneS Inc, Ansan-si, Gyeonggi-do, South Korea.
Cell Prolif. 2022 Nov;55(11):e13305. doi: 10.1111/cpr.13305. Epub 2022 Jul 6.
Ameloblastoma (AM) has been known as a benign but locally invasive tumour with high recurrence rates. Invasive behaviour of the AM results in destruction of the adjacent jawbone and the non-detectable remnants during surgery, interrupting the complete elimination of cancer cells.
To explore novel targets for the tumour cell invasion, a transcriptomic analysis between AM and odontogenic keratocyst were performed through next-generation sequencing in detail.
Enrichment of CACNA1C gene (encoding Cav1.2) in AM, a subunit of the L-type voltage-gated calcium channel (VGCC) was observed for the first time. The expression and channel activity of Cav1.2 was confirmed by immunostaining and calcium imaging in the patient samples or primary cells. Verapamil, L-type VGCC blocker revealed suppression of the Ca -induced cell aggregation and collective invasion of AM cells in vitro. Furthermore, the effect of verapamil in suppressing AM invasion into the adjacent bone was confirmed through orthotopic xenograft model specifically.
Taken together, Cav1.2 maybe considered to be a therapeutic candidate to decrease the collective migration and invasion of AM.
成釉细胞瘤（AM）是一种良性但具有局部侵袭性的肿瘤，复发率较高。AM 的侵袭性行为导致相邻颌骨破坏和手术过程中无法检测到残留，从而中断了癌细胞的完全消除。
为了探索肿瘤细胞侵袭的新靶点，我们通过下一代测序对 AM 和牙源性角化囊肿进行了详细的转录组分析。
首次观察到 L 型电压门控钙通道（VGCC）亚基 CACNA1C 基因（编码 Cav1.2）在 AM 中的富集。通过免疫染色和钙成像在患者样本或原代细胞中证实了 Cav1.2 的表达和通道活性。维拉帕米，L 型 VGCC 阻滞剂，体外抑制了 AM 细胞诱导的钙诱导的细胞聚集和集体侵袭。此外，通过特定的原位异种移植模型证实了维拉帕米抑制 AM 侵袭相邻骨骼的效果。
综上所述，Cav1.2 可被视为一种治疗候选药物，以减少 AM 的集体迁移和侵袭。
