Our findings indicate that PEDF decreases the metastatic potential of NSCLC cells through regulation of THBS1 release in cancer cell-derived exosomes, thus uncovering a new mechanism of lung cancer progression.
The high sensitivity and specificity of E-Cadherin brain angiogenesis inhibitor 1 and thrombospondin-1 were also confirmed in early lung cancer analysis.
THBS1 was in general underexpressed in lung cancer; in contrast, mRNA levels of THBS2 were markedly overexpressed in a number of datasets of non-small cell lung carcinoma (NSCLC), including lung adenocarcinoma (AC) and squamous cell carcinoma.
Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy.
Previous studies demonstrated that metastatic MDA-MB-435 breast carcinoma cells synthesized and secreted less of the extracellular matrix protein thrombospondin 1 (TSP1) than nonmetastatic breast carcinoma cell lines, a trend also observed for melanoma and lung carcinoma cell lines.