Development of a novel murine model of lymphatic metastasis

Clin Exp Metastasis. 2020 Apr;37(2):247-255. doi: 10.1007/s10585-020-10025-3. Epub 2020 Feb 12.

Abstract

Current laboratory models of lymphatic metastasis generally require either genetically modified animals or are technically challenging. Herein, we have developed a robust protocol for the induction of intralymphatic metastasis in wild-type mice with reproducible outcomes. To determine an optimal injection quantity and timeline for tumorigenesis, C57Bl/6 mice were injected directly into the mesenteric lymph duct (MLD) with varying numbers of syngeneic murine colon cancer cells (MC38) or gastric cancer cells (YTN16) expressing GFP/luciferase and monitored over 2-4 weeks. Tumor growth was tracked via whole-animal in vivo bioluminescence imaging (IVIS). Our data indicate that the injection of tumor cells into the MLD is a viable model for lymphatic metastasis as necropsies revealed large tumor burdens and metastasis in regional lymph nodes. This protocol enables a closer study of the role of lymphatics in cancer metastasis and opens a window for the development of novel approaches for treatment of metastatic diseases.

Keywords: Colon cancer; Gastric cancer; Intralymphatic; Luciferase; Mesenteric lymph duct.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor / transplantation
  • Colonic Neoplasms / pathology*
  • Disease Models, Animal*
  • Female
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Luciferases / chemistry
  • Luciferases / genetics
  • Luciferases / metabolism
  • Luminescent Measurements
  • Lymph Nodes / diagnostic imaging
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / diagnostic imaging*
  • Lymphatic Metastasis / pathology
  • Lymphatic Vessels
  • Male
  • Mesentery
  • Mice
  • Mice, Inbred C57BL
  • Stomach Neoplasms / pathology*
  • Tomography, Optical
  • Tumor Burden

Substances

  • Green Fluorescent Proteins
  • Luciferases