An orthotopic mouse model of gastric cancer invasion and metastasis

Sci Rep. 2018 Jan 16;8(1):825. doi: 10.1038/s41598-017-19025-y.

Abstract

Gastric cancer is a leading cause of cancer death worldwide, with advanced stage being correlated to the level of tumour invasion and metastasis. Current research is heavily focused on the identification and development of efficacious therapeutics targeting these fundamental hallmarks of cancer, however there are currently no animal models that mimic the invasive phenotypes observed in humans. To address this we have developed an orthotopic mouse model whereby gastric cancer cell lines are tagged with luciferase and injected into the subserosal layer of the stomach. This allows for the monitoring of primary tumour growth and metastasis in real-time as well as quantitation of the degree of tumour invasion through the stomach wall by immunohistochemistry. We have three models based on the degree of invasion and metastasis that are cell line specific: The AGS cells develop into invasive tumours by 4-weeks with no evidence of metastases, MKN45 cells are moderately metastatic with minimal invasion till week 2 and MKN28 cells are highly metastatic and fully invasive by week 1. These models have utility as a tool for testing the efficacy of anti-tumour, anti-invasive and anti-metastatic therapies in the setting of gastric cancer, which currently has poor treatment options.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Neoplasms / pathology
  • Abdominal Neoplasms / secondary
  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Knockout
  • Mucous Membrane / pathology
  • Neoplasm Invasiveness
  • Optical Imaging
  • Stomach Neoplasms / diagnostic imaging
  • Stomach Neoplasms / pathology*
  • Thoracic Neoplasms / pathology
  • Thoracic Neoplasms / secondary
  • Transplantation, Heterologous