Modeling liver metastasis using a tumor cell line derived from an enhanced green fluorescent protein transgenic mouse.

Abstract

The liver is a common repository for metastases, second only to lymph nodes. The majority of gastrointestinal cancer deaths are attributed to liver metastasis. Researchers have widely used stable transfection of green florescent protein (GFP) to track tumor cells in the liver metastasis cascade. However, stable, sustained GFP expression in these tumor cells requires proper drug selection to avoid its loss in animal models. To overcome this, we generated a pancreatic tumor cell line that stably expressed enhanced GFP (EGFP). First, we induced a pancreatic tumor by administering 3-methylcholanthrene in the pancreas of an EGFP transgenic mouse, which had stable ubiquitous EGFP expression. Second, we established the parental pancreatic cancer cell line LG as a culture from a tumor. Third, we selected the cell line LG-L7, a highly liver-metastatic variant of LG. Both LG and LG-L7 cells exhibited a stable EGFP genotype and constant EGFP protein expression both in vitro and in vivo. Also, we could track disseminated LG cells at the single-cell level in vivo. Therefore, this novel cell model system is a useful tool for studying tumor-cell dissemination and metastasis, their underlying mechanisms, and potential therapeutic approaches for them.