Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice

Abstract

Colorectal cancer cells can transfer the oncogene KRAS to distant cells, predisposing them to malignant transformation (Genometastasis Theory). This process could contribute to liver metastasis; besides, hepatic progenitor cells (HPCs) have been found to be involved in liver malignant neoplasms. The objective of this study is to determine if mouse HPCs—Oval cells (OCs)—are susceptible to incorporate Kras GAT (G12D) mutation from mouse colorectal cancer cell line CT26.WT and if OCs with the incorporated mutation behave like malignant cells. To achieve this, three lines of OCs in diferent conditions were exposed to CT26.WT cells through transwell co-culture for a week. The presence of KrasG12D and capacity to form tumors were analyzed in treated samples by droplet digital PCR and colony-forming assays, respectively. The results showed that the KrasG12D mutation was detected in hepatic culture conditions of undiferentiated OCs and these cells were capable of forming tumors in vitro. Therefore, OCs are susceptible to malignant transformation by horizontal transfer of DNA with KrasG12D mutation in an undiferentiated condition associated with the liver microenvironment. This study contributes to a new step in the understanding of the colorectal metastatic processTis study was supported by Conchita Rábago Foundation, Madrid, Spain by a doctoral scholarship to Rocío Olivera-Salazar, Instituto de Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) (PI20/01052), Instituto de Salud Carlos III (ISCIII), and Spanish Network of Cell Terapy (TerCel) (RD16/0011/0013)