Visualizing the distribution of cancer-derived exosomes at the cellular level

Tumor-derived exosomes play important roles in tumor metastases. In this report, researchers at Gifu University School of Medicine observed the fate of tumor-derived exosomes in pancreatic cancer metastatic nude-mouse models using color-coded imaging. 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. 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.

Mia-PaCa-2 cells in liver metastasis contained GFP-expressing exosomes

(A) RFP-labeled Mia-Paca-2 cells producing GFP-labelled exosomes in liver metastases (yellow arrows). GFP expressing exosomes are present in metastasis (Bar=30 μm). (B) Blue arrows indicate GFP-exosomes incorporated in RFP-labeled Mia-Paca-2 cells. Yellow arrows indicate macrophages in liver containing tumor-derived exosomes (Bar=30 μm).