Cancer cells are known to secrete exosomes with pro-metastatic effects. Pancreatic-cancer-derived exosomes are now shown to promote liver metastasis by eliciting pre-metastatic niche formation through a multi-step process. This involves uptake of exosome-derived factors by liver Kupffer cells and hepatic stellate cell activation to generate a fibrotic microenvironment with immune cell infiltrates that favours metastasis.
To form metastases at a distal organ, cancer cells have to successfully complete a series of distinct steps, which include invasion through the basement membrane, intravasation into the bloodstream, dissemination through the circulation, extravasation to the distal tissue parenchyma and adaptation to the foreign microenvironment. Although the majority of disseminated cells fail to survive and proliferate after reaching a foreign tissue, metastatic disease causes the death of approximately 90% of cancer patients. Therefore, understanding the mechanisms through which certain cancer cells are able to grow at metastatic sites is a topic of high clinical importance…
The sequential steps in liver pre-metastatic niche formation induced by PDAC-derived exosomes