Department of Interventional Radiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Mol Med Rep. 2018 Dec;18(6):5087-5094. doi: 10.3892/mmr.2018.9500. Epub 2018 Sep 20.
Pancreatic cancer (PaC) is an aggressive malignancy, which is associated with high levels of metastasis. Circulating tumor cells (CTCs), which may be considered a functional biomarker and promising treatment strategy for metastasis, are associated with the prognosis and progression of various metastatic cancers, including PaC. Receptor tyrosine kinase‑like orphan receptor 1 (ROR1) expression contributes to cell metastasis and poor clinical outcomes in malignant tumors. The present study aimed to explore the function of ROR1 in PaC CTCs. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to examine the expression of ROR1, E‑cadherin and N‑cadherin. Cell proliferative and invasive ability was assessed by MTT and Transwell assays, respectively. The results revealed that the mRNA and protein expression levels of ROR1 were augmented in PaC tissues. Furthermore, the mRNA expression levels of ROR1 were higher in CTCs compared with in peripheral blood cells, and ROR1 was more highly expressed in CTCs than in cells. Notably, CTCs exhibited a markedly greater proliferative and invasive capacity than PANC‑1 and SW‑1990 cells, whereas knockdown of endogenous ROR1 by small interfering RNA led to suppression of the invasion of CTCs. In addition, it was revealed that the mechanism underlying the effects of ROR1 on PaC CTC metastasis may involve the epithelial‑mesenchymal transition process. In conclusion, ROR1 may be considered a potential biomarker and therapeutic target for the treatment of PaC.
胰腺癌(PaC)是一种侵袭性恶性肿瘤,其与高水平的转移相关。循环肿瘤细胞(CTC)可被视为一种功能性生物标志物,并且可能是转移性癌症(包括 PaC)的一种有前途的治疗策略。受体酪氨酸激酶样孤儿受体 1(ROR1)的表达可促进肿瘤细胞的转移并导致恶性肿瘤的不良临床结局。本研究旨在探索 ROR1 在 PaC CTC 中的功能。采用逆转录-定量聚合酶链反应和 Western blot 分析检测 ROR1、E-钙黏蛋白和 N-钙黏蛋白的表达。通过 MTT 和 Transwell 测定分别评估细胞的增殖和侵袭能力。结果表明,ROR1 的 mRNA 和蛋白表达水平在 PaC 组织中增加。此外,与外周血细胞相比,ROR1 在 CTCs 中的 mRNA 表达水平更高,并且在 CTCs 中的表达水平高于细胞。值得注意的是,与 PANC-1 和 SW-1990 细胞相比,CTCs 表现出更强的增殖和侵袭能力,而通过小干扰 RNA 敲低内源性 ROR1 可抑制 CTCs 的侵袭。此外,研究揭示了 ROR1 对 PaC CTC 转移的影响的机制可能涉及上皮-间充质转化过程。综上所述,ROR1 可被视为治疗 PaC 的潜在生物标志物和治疗靶点。