Microenvironmental control of sortilin exosomes in lung cancer

Abstract

Lung cancer, despite medical advancement, is still the most common form of cancer, and contributes to the highest incidence rate of mortality of all cancer types. Sortilin, through the use of exosome-based cell-cell communication may play an important role in the way that cancer progression takes place. Cell invasion assays revealed that in sortilin knockdown cells, invasion rates are reduced significantly, and upon the introduction of exosomes derived from cells overexpressing sortilin, invasion rates are restored to that of the wild type cells. Additionally, sortilin overexpression from exosomes dramatically raised cell proliferation rates compared to standard wild types. The addition of exosomes derived from overexpressing sortilin cells revealed that induced sortilin expression in knockdown cells was likely to be as a result of miRNA cargo from the exosome over transported proteomic sortilin between cells. NF-κB cleavage was observed over time upon treatment of exosomes derived from cells overexpressing sortilin in sortilin knockdown cells. The results indicate that sortilin plays a role in the invasion rate of lung cancer cells, and suggests that exosomal control of sortilin expression is controlled via miRNA cargo and holds influence in the tumorigenic properties of cancer cells in culture.

Date of Award	2019
Original language	English