The Role of Exosomes in Cancer Metastasis

Exosomes are small membrane vesicles with a size ranging from 40-100nm. They can serve as functional mediators in cell interaction leading to cancer metastasis.

Most studies of the pathogenesis of metastasis focus on genetic or phenotypic changes of the cancer cell itself, however, there is growing evidence that cancer cells communicate with each other and the surrounding stroma leading to metastasis. Metastasis is a multistep process including invasion of the tumor cell through the basal membrane and into blood vessels, survival in the blood circulation, attachment to the blood vessels, extravasation and at last colonization and growth in the host organ. Cells can communicate with various types of extracellular membrane vesicles. These include exosomes, proteasomes, apoptotic blebs and microvesicles. Since exosomes can promote a variety of intratumoral biological processes, it seems likely that they can also influence metastatic properties of malignant tumors.

Researchers from the Medical University of Innsbruck highlight the role of exosomes in the various steps of the metastatic cascade and how exosome dependent pathways can be targeted as therapeutic approach or used for liquid biopsies.

Organotropic metastatic growth and premetastatic niche formation

Tumor derived exosomes (TDEs) are distributed to the specific metastatic sites via integrins. ITGβ4 promotes lung tropism and ITGβ5 promotes liver tropism. TDEs prepare the metastatic organ to form a premetastatic niche, with the help of immigrating bone marrow derived progenitor cells (BMDCs). TDEs promote education and mobilization of BMDCs that support tumor vasculogenesis, invasion and metastasis. TDEs recruit BMDCs through upregulation of proinflammatory molecules, like miR-122, S100 and fibronectin, and enhance vascular leakiness at the metastatic sites. After premetastatic niche formation cancer cells can invade the distant organ, begin colonialization and form organspecific metastasis.