ROR1 is highly expressed in circulating tumor cells and promotes invasion of pancreatic cancer

Mol Med Rep. 2018 Dec;18(6):5087-5094. doi: 10.3892/mmr.2018.9500. Epub 2018 Sep 20.

Abstract

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.

Keywords: pancreatic cancer; circulating tumor cells; receptor tyrosine kinase-like orphan receptor 1; cell proliferation; epithelial-mesenchymal transition; cell invasion.

MeSH terms

  • Adult
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplastic Cells, Circulating / metabolism*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Receptor Tyrosine Kinase-like Orphan Receptors / genetics*

Substances

  • Biomarkers, Tumor
  • ROR1 protein, human
  • Receptor Tyrosine Kinase-like Orphan Receptors