Color-coded Imaging of the Fate of Cancer-cell-derived Exosomes During Pancreatic Cancer Metastases in a Nude-mouse Model

Anticancer Res. 2019 Aug;39(8):4055-4060. doi: 10.21873/anticanres.13561.

Abstract

Background/aim: Tumor-derived exosomes play important roles in tumor metastases. In this report, we observed the fate of tumor-derived exosomes in pancreatic cancer metastatic nude-mouse models using color-coded imaging.

Materials and methods: Mia-PaCa-2 human pancreatic cancer cells expressing red fluorescent protein (RFP) were transduced by exosome-specific pCT-CD63-green fluorescent protein (GFP) and injected in the spleen of nude mice.

Results: Four weeks after injection of these cells into the spleen, liver metastases developed and tumor-derived exosomes were observed within the metastatic cancer cells and in Kupffer cells. Furthermore, tumor-derived exosomes diffused to bone marrow and lung cells, especially macrophages, without any metastases present.

Conclusion: In the present study, we visualized the distribution of cancer-derived exosomes for the first time at the cellular level, in a pancreatic-cancer metastatic model.

Keywords: Pancreatic cancer; color-coded imaging; exosomes; green fluorescent protein; macrophage; nude mice; red fluorescent protein; tumor-derived exosomes.

MeSH terms

  • Animals
  • Cell Lineage / genetics*
  • Disease Models, Animal
  • Exosomes / genetics*
  • Green Fluorescent Proteins / chemistry
  • Humans
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Luminescent Proteins / chemistry
  • Mice
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Red Fluorescent Protein
  • Tumor Microenvironment / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Luminescent Proteins
  • Green Fluorescent Proteins