Abstract
Glypican-3 (GPC3) is considered as a cell surface heparan sulfate proteoglycan. It is overexpressed in skin cancer and promotes tumor progression and pathogenicity. Therefore, we aimed to find out the therapeutic effects of immuno-suppressing GPC3 in skin cancer experimentally induced in mice as well as to underline molecular mechanisms especially inflammatory and apoptotic pathways. Skin cancer was experimentally induced in mice by repeated rubbing of mice skin with 7,12-dimethylbenz (a) anthracene. Mice were injected with anti-GPC3. Skin samples were isolated to investigate the gene and protein expression of GPC3, Wnt-1, NF kappa B, TNF-alpha, IGF-1, p38 MAPK and caspase-3 using PCR, Western blot and ELISA. Moreover, skin sections were stained with hematoxylin and eosin. Treating skin cancer mice with anti-GPC3 significantly blocked GPC3, which is accompanied by amelioration of skin cancer-induced increase in the numbers of tumors and scratching behavior. Moreover, anti-GPC3 attenuated skin cancer-induced increase in the expression of Wnt-1, NF kappa B, TNF-alpha, IGF-1, p38 MAPK and caspase-3. In parallel, anti-GPC3 reduced degeneration of melanocyte cells and reduced phagocytic cells epidermal hyperplasia and dysplasia in skin sections stained with hematoxylin and eosin stain. In conclusion, anti-GPC3 produced anti-tumor effects against skin cancer, which can be explained by reduction in both inflammatory and apoptotic pathways. Targeting GPC3 is a promising therapeutic approach for skin cancer. Graphic abstract