This study aimed to characterize exosomes present in the serum of patients diagnosed with Lymphangioleiomyomatosis (LAM), a rare and low-grade neoplasm predominantly affecting females.  Exosomes have been found to play important roles in disease progression and have diagnostic and disease-monitoring potential. Serum from LAM patients have increased numbers of exosomes compared to serum samples from healthy controls. Particle counts are negatively correlated with the forced expiratory volume (FEV1) (r=-0.4667; p-value=0.0295) in LAM patients. We also assessed the metalloproteinase activity of the exosomes by zymography. Interestingly, these LAM-derived exosomes had significantly higher activity of Pro-MMP-9.

Increased expression of vimentin, a major marker of EMT, and an increased invasive capacity (respectively 1.4- and 2.2-fold change) were observed in A549 cells treated with LAM-derived exosomes compared to healthy controls. Analysis of the LAM Single Cell Atlas showed an 8-fold increased expression of TWIST1, a key transcription factor for EMT, and was uniquely expressed in 'LAM cells', which had metastasized. Proteomic analysis revealed high expression of C3 and C5 (respectively 1.4- and 2.1-fold change; p=0.0276 and p=0.0034) in LAM-derived exosomes suggesting the potential regulatory role of the complement system in the EMT mediated by exosomes.

These results highlight the importance of further investigation into the potential involvement of exosomes in the metastatic spread of LAM cells and their influence on the innate and adaptive immune response to the invasion.