Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Cancer Lett. 2017 Apr 1;390:103-114. doi: 10.1016/j.canlet.2017.01.008. Epub 2017 Jan 16.
Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with pancreatic ductal adenocarcinoma (PDAC). Kindlin-2 is a focal adhesion protein that regulates the activation of integrins. This study aimed to clarify the role of kindlin-2 in PSCs in pancreatic cancer. Kindlin-2 expression in 79 resected pancreatic cancer tissues was examined by immunohistochemical staining. Kindlin-2-knockdown immortalized human PSCs were established using small interfering RNA. Pancreatic cancer cells were treated with conditioned media of PSCs, and the cell proliferation and migration were examined. SUIT-2 pancreatic cancer cells were subcutaneously injected into nude mice alone or with PSCs and the size of the tumors was monitored. Kindlin-2 expression was observed in PDAC and the peritumoral stroma. Stromal kindlin-2 expression was associated with shorter recurrence-free survival time after R0 resection. Knockdown of kindlin-2 resulted in decreased proliferation, migration, and cytokine expression in PSCs. The PSC-induced proliferation and migration of pancreatic cancer cells were suppressed by kindlin-2 knockdown in PSCs. In vivo, co-injection of PSCs increased the size of the tumors, but this effect was abolished by kindlin-2 knockdown in PSCs. In conclusion, kindlin-2 in PSCs promoted the progression of pancreatic cancer.
胰腺星状细胞（PSCs）在与胰腺导管腺癌（PDAC）相关的胰腺纤维化中起着关键作用。Kindlin-2 是一种黏着斑蛋白，可调节整合素的激活。本研究旨在阐明 Kindlin-2 在胰腺癌细胞中的 PSCs 中的作用。通过免疫组织化学染色检查了 79 例切除的胰腺癌组织中的 Kindlin-2 表达。使用小干扰 RNA 建立了 Kindlin-2 敲低的永生化人 PSCs。将胰腺癌细胞用 PSCs 的条件培养基处理，并检查细胞增殖和迁移。将 SUIT-2 胰腺癌细胞单独或与 PSCs 皮下注射到裸鼠中，并监测肿瘤的大小。在 PDAC 和肿瘤周围基质中观察到 Kindlin-2 的表达。基质 Kindlin-2 的表达与 RO 切除后无复发生存时间较短有关。Kindlin-2 的敲低导致 PSCs 中增殖、迁移和细胞因子表达减少。PSCs 中的 Kindlin-2 敲低抑制了胰腺癌细胞的增殖和迁移。在体内，PSCs 的共注射增加了肿瘤的大小，但这种作用被 PSCs 中的 Kindlin-2 敲低所消除。总之，PSCs 中的 Kindlin-2 促进了胰腺癌的进展。
