Emergency Department, The First Hospital of Jilin University, Jilin University, Changchun, China.
Department of Otolaryngology Head and Neck Surgery, The First Hospital of Jilin University, Jilin University, Changchun, China.
Neoplasma. 2021 Jan;68(1):174-179. doi: 10.4149/neo_2020_200803N811. Epub 2020 Oct 22.
Activated pancreatic stellate cells (PSCs) with an increased proliferation and migration ability are the partners in crime with pancreatic cancer cells. Acid-sensing ion channel 1 (ASIC1) is expressed in pancreatic cancer and PSCs, and especially, it mediates the activation of PSCs. However, whether ASIC1 is involved in pancreatic cancer cells-induced biological behavior re-educating of PSCs is unclear. In this study, the change of ASIC1 expression in PSCs and pancreatic cancer Panc-1 cells after in-direct co-culture was detected by western blotting, and the proliferation and migration of PSCs with ASIC1 knockdown under Panc-1 cells-conditioned medium (Panc-1-CM) was assessed. The results showed that pancreatic cancer cells induced ASIC1 overexpression, and the enhanced proliferation and migration of PSCs was weakened by ASIC1 inhibition. In addition, the extracellular signal-regulated kinase (ERK) expression in PSCs remained stable, but the phosphorylated ERK (p-ERK) expression in PSCs treated with Panc-1-CM increased, which was suppressed by ASIC1 knockdown. These results indicate that ASIC1 participates in the regulation of PSCs proliferation and migration induced by cancer cells via the ERK pathway, and ASIC1 inhibition may be beneficial to pancreatic cancer treatment.
活化的胰腺星状细胞（PSCs）具有增殖和迁移能力增强的特点，是与胰腺癌细胞狼狈为奸的伙伴。酸感应离子通道 1（ASIC1）在胰腺癌和 PSCs 中表达，特别是介导 PSCs 的激活。然而，ASIC1 是否参与胰腺癌细胞诱导的 PSCs 生物学行为再教育尚不清楚。在这项研究中，通过 Western blot 检测间接共培养后 PSCs 和胰腺癌 Panc-1 细胞中 ASIC1 表达的变化，并评估 ASIC1 敲低后在 Panc-1 细胞条件培养基（Panc-1-CM）下 PSCs 的增殖和迁移情况。结果表明，胰腺癌细胞诱导 ASIC1 过表达，ASIC1 抑制减弱了 PSCs 的增殖和迁移增强。此外，Panc-1-CM 处理的 PSCs 中细胞外信号调节激酶（ERK）表达保持稳定，但磷酸化 ERK（p-ERK）表达增加，ASIC1 敲低抑制了 p-ERK 表达。这些结果表明，ASIC1 通过 ERK 通路参与调节癌细胞诱导的 PSCs 增殖和迁移，ASIC1 抑制可能有益于胰腺癌的治疗。
