ITGA5 inhibition in pancreatic stellate cells re-educates the in vitro tumor-stromal crosstalk.

The interaction between pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs) promotes aggressive progression of pancreatic cancer, and disrupting the tumor-stromal crosstalk is a promising therapeutic strategy. Integrin α5 (ITGA5) is specifically overexpressed in pancreatic cancer stroma and activated PSCs. ITGA5 acts as a mediator in PCCs-PSCs interaction, but its role in regulating biological behaviors of PSCs and PCCs is still not quite clear. In this study, ITGA5 in PSCs was inhibited using its specific inhibitor AV3 peptide or siRNA knockdown technique. Pancreatic cancer SW1990 cells conditioned medium (SW1990-CM) and an indirect co-culture system were used to mimic the environment of the in vitro tumor-stromal crosstalk. Our results showed that ITGA5 inhibition impaired the proliferation and migration of PSCs, but enhanced autophagy. After co-culture with PSCs, SW1990 cells gained some cancer stem cells (CSCs)-like characteristics, such as increased drug resistance, migration and invasion ability, but PSCs with ITGA5 knockdown were incapable of producing these effects. The present results suggested that ITGA5 was involved in the development of the malignant biological behaviors of PSCs and PCCs, and ITGA5 inhibition in PSCs might benefit the treatment of pancreatic cancer by re-educating PCCs-PSCs interaction.