Pancreatic carcinoma cells colonizing the liver modulate the expression of their extracellular matrix genes
| Autor: | Irina Berger, Khamael M.K. Al-Taee, Martin R. Berger, Michael Zepp, Hassan Adwan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Gene knockdown MMP2 ASML cell line extracellular matrix pancreatic ductal adenocarcinoma Transfection Biology Cell biology CCL20 03 medical and health sciences liver metastasis 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Gene expression microRNA Genetics mRNA and miRNA expression DNA microarray Gene Research Paper |
| Zdroj: | Genes & Cancer |
| ISSN: | 1947-6019 |
| Popis: | Liver is the main target of pancreatic ductal adenocarcinoma (PDAC) metastasis. Here, a rat model was used for analysing gene expression modulations during liver colonization. ASML PDAC cells were injected to isogenic rats and re-isolated at various stages of liver colonization for RNA isolation or re-cultivation. Microarrays were used for analysing mRNA and miRNA profiles of expres-sion. The results were partially confirmed by (q) RT-PCR and western blot. Selected genes were knocked down by siRNA transfection and the resulting cell behaviour was analysed. The ratio of up- and down regulated genes decreased from 20:1 (early stage) to 1.2:1 (terminal stage). Activation of cancer relevant gene categories varied between stages of liver colonization, with a nadir in the intermediate stage. The cells' environment triggered up to hundredfold changed expression for collagens, matrix metalloproteinases and chemokines. These modulations in mRNA expression were related to respective changes at miRNA levels. Gene expression knockdown of Mmp2 and Ccl20, which were highly modulated in vivo, was correlated with reduced prolif-eration and migration in vitro. Thus, target genes and temporal alterations in expression were identified, which can serve as basis for future therapeutic or diagnostic purposes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|