Pancreatic cancer is one of the most lethal diseases in the world, with five-year-survival rate less than 9%. The poor prognosis of pancreatic cancer is related to several factors, including the early occurrence of metastatic disease. Only 20% of patients who are in a non-metastatic stage have chance to receive curative surgery, while the remainder are not eligible for surgery in an advanced or metastatic stage. It is therefore necessary to explore the mechanisms responsible for metastasis of pancreatic cancer to allow the development of effective therapeutic strategies. However, we lack effective models mimic the process of metastasis in vitro currently, which hinders our study on the molecular mechanism of tumor metastasis to some aspect.
On 13th March, 2019, the team of Pro. Yupei Zhao published an article in Science China Life Sciences entitled "Integrated analysis of gene expression and methylation profiles of novel pancreatic cancer cell lines with highly metastatic activity". This research established two human pancreatic cancer cell sublines with high metastasis potential, MIA PaCa-2 In8 and Panc-1 In8, by Matrigel induction assay. The established cell lines showed increased migration, invasion, wound-healing, and clonogenic abilities, compared with their parental cells in vitro. Following tail-vein injection in mouse models of lung metastasis, these two highly metastatic cell lines also demonstrated increased aggressiveness in vivo.
In addition, differential expression of mRNA, long non-coding RNA (lncRNA), micro RNA (miRNA), and methylation profiling were compared between the highly metastatic and parental cell lines, and the signaling pathways involved in the metastatic processes were also analyzed. A dysregulated lncRNA-miRNA-mRNA competitive endogenous RNAs (ceRNAs) network was constructed based on the above data, providing valuable material for future research on mechanisms.
It is worth mentioning that, although some highly metastatic pancreatic cancer cell lines have been reported previously, only few studies have established highly metastatic pancreatic cancer cell lines by induction. In the current study, researchers induced the invasion and migration abilities of two different pancreatic cancer cell lines, MIA PaCa-2 and Panc-1, using Matrigel, which consists of laminin, transforming growth factor-β, collagen IV, fibroblast growth factor, tissue fibroblast activating factor, and other growth factors, to mimic the extracellular matrix in vivo. Compared with previous methods that induced highly metastatic cancer cells in situ or in the caudal vein in vivo, this method achieved the same effect but was easier and more convenient.
In conclusion, the study established two highly metastatic pancreatic cancer lines, MIA PaCa-2 In8 and Panc-1 In8, from parental cell lines by Matrigel induction assay, and analyzed and compared the integrated mRNA, lncRNA, miRNA, and methylation profiles between the highly metastatic and parental cell lines, providing functional tools and solid material for future studies.
Yang G, Wang HY, Feng MY, You L, Zheng LF, Zhang TP, Cong L, Zhao YP (2019) Integrated analysis of gene expression and methylation profiles of novel pancreatic cancer cell lines with highly metastatic activity. Sci China Life Sci, doi: 10.1007/s11427-018-9495-2 http://engine.