In vivo trafficking of cancer-derived exosomes and their role in metastasis

Cancer metastasis is one of the leading causes of cancer-related mortality. This process is driven by a combination of biological processes including invasion, intravasation, circulation, extravasation, and colonization of distant organs, among which cancer cell-derived exosomes facilitate metastasis through their enriched oncogenic miRNAs and lncRNAs to enhance cancer cell migration and invasion, promote epithelial-mesenchymal transition in recipient cells, help cancer cells evade immune detection, and alter the microenvironment to promote the formation of a pre-metastatic niche. While the role of cancer exosomes in various metastatic processes has been extensively studied, the exosomal trafficking of cancer cell-derived exosomes has not been thoroughly reviewed. This review describes the dynamics between cancer cell-derived exosomes and various cellular components in blood and lymph circulation during cancer metastasis. Additionally, we emphasize the role of cancer exosomes in establishing pre-metastatic niches and in promoting metastasis to secondary sites. By offering a thorough review of exosome trafficking in cancer metastasis, this review may potentially help the future identification of treatment targets for metastasis inhibition.