Anti-angiogenic and anti-metastatic effects of PEDF overexpression in anaplastic thyroid cancer cells: A preliminary in vitro study

Pigment epithelium-derived factor (PEDF) is a potent endogenous immunomodulatory protein with anti-metastatic, anti-angiogenic, and anti-inflammatory properties, and has recently gained attention for its ability to target tumor cells across various cancers. However, the molecular mechanism underlying the effects of PEDF on angiogenesis and metastasis in anaplastic thyroid cancer (ATC), one of the most lethal and aggressive human malignancies, remains poorly understood. In this study, the PEDF coding sequence was cloned into a lentiviral backbone plasmid vector, and its effects on metastasis and epithelial-to-mesenchymal transition (EMT) were assessed in 8305C ATC cells using RT-qPCR, migration, invasion, doubling time, wound healing assays, as well as western blot analysis. Angiogenesis was evaluated using the chicken chorioallantoic membrane (CAM) assay. Overexpression of PEDF in 8305C cells significantly reduced the expression of VEGF and HIF-1α, downregulated angiogenesis-related genes, and was associated with reduced expression of PI3K/AKT-related genes. Additionally, PEDF overexpression markedly decreased MMP-9 and MMP-2 levels, leading to reduced invasion, migration, and EMT-associated phenotype. These findings suggest that PEDF overexpression is associated with reduced angiogenic and metastatic phenotypes in ATC cells and warrants further investigation in additional preclinical models.