Few genes are associated with the capability of pancreatic ductal adenocarcinoma cells to grow in the liver of nude rats

Abstract

Owing to aggressiveness and chemoresistance, pancreatic ductal adenocarcinoma (PDAC) is characterised by a poor prognosis. To address this disease-spe-cific dilemma we aimed to establish animal models, which can be used for identifying new specific tumor markers, as well as serving as tools for potential therapeutic approaches. From a panel of sixteen pancreatic cancer cell lines, two human (Suit2-007 and Suit2-013) and a rat (ASML) cell line were selected for their properties to grow in the liver of male RNU rats and mimic liver metastasis of PDAC. For better monitoring of metastatic tumor growth in vivo, all three pancreatic cancer cell lines were stably transfected with eGFP and luciferase marker genes. In addition, the mRNA expression profile of 13 human PDAC cell lines was analyzed by BeadChip array analysis. Only 33 genes and 5 signaling pathways were identified as significantly associated with the ability of the cell lines to grow initially and/or consistently in rat liver. Only a minority of these genes (osteopontin, matrix metalloproteinase-1 and insulin-like growth factor 1) has been intensively studied and shown to be closely related to cancer progression. The function of the remaining 30 genes ranges from moderate to poorly investigated, and their function in cancer progression is still unclear. The ensuing three pancreatic cancer liver metastasis models vary in their aggressiveness and macroscopic growth. They will be used for preclinical evaluation of new therapeutic approaches aiming at the genes identified.

Riproximin’s activity depends on gene expression and sensitizes PDAC cells to TRAIL

“…This model is based on the rat PDAC cell line ASML, which was injected intra-portally to mimic the natural way of liver metastasis by PDAC cells, as described previously. 17,24 The effect of Rpx in this model was significant in terms of tumor growth reduction as shown for colorectal cancer liver metastasis before.…”

“…For mimicking PDAC liver metastasis, ASML cells, which had been transfected with the reporter genes eGFP and luciferase 17 were implanted intra-portally to BDX rats. One week after tumor cell transplantation, all rats showed clearly visible tumor growth.…”

Synergistic Anti-proliferative Effects of Cucurbitacin I and Irinotecan on Human Colorectal Cancer Cell Lines

“…As a result of this cancer cells are not indestructible enough [41]. Moreover, some drug combinations show strong synergism that helps to achieve the same therapeutic effect with lower dose and, hence, less toxicity [34][35][36][37][38][39][40][41][42]. Some reports have shown that cucurbitacins show a synergistic effect with chemotherapeutic agents that are already established in the treatment of human cancers [38][39][40][41][42].…”

“…Although initial attention to cucurbitacin as a potential anticancer drug withered for decades, recent discoveries showing that cucurbitacin is a strong STAT3 inhibitor have reclaimed the attention of the drug industry one more time [22,34]. The molecular landscape of colorectal cancer is complex.…”

“…Optical density was measured at a 570 nm wavelength using an ELISA plate reader (BioTec, USA). MTT assay was determined by the method described by Eyol [34] with some minor modifications.…”