Exosomal Leucine-rich-alpha2-glycoprotein 1 Derived from Non-Small-Cell Lung Cancer Cells Promotes Angiogenesis via Transforming-growth-factor-beta Signal Pathway

Non-small-cell lung cancer (NSCLC) is a major cause for cancer-related deaths around the globe, partially due to the frequent recurrence and metastasis. Leucine-rich-alpha2-glycoprotein 1 (LRG1) is reportedly upregulated in several cancers including NSCLC; however, its functions in NSCLC remain elusive. We used quantitative real-time PCR and western blot assays to evaluate the expression patterns of LRG1 in tumor tissues collected from NSCLC patients, as well as NSCLC cell lines, and examined the effects of LRG1 on the proliferation, migration, and invasion of NSCLC cells. Further, we isolated exosomes from the blood of NSCLC patients, as well as NSCLC cell cultures, and assessed the impact of exosome exposure on the angiogenic capacities of human umbilical vein endothelial cells. LRG1 was upregulated in NSCLC tissues and cells and induced an enhancement of NSCLC cell proliferation, migration, and invasion. In addition, LRG1 was enriched in the exosomes derived from NSCLC tissue and cells, and mediated a proangiogenic effect via the activation of transforming growth factor β (TGF-β) pathway. Exosomal LRG1 derived from NSCLC cells promotes angiogenesis via TGF-β signaling and possesses the potential of a therapeutic target in NSCLC treatment.