Provided herein are agents that inhibit the function (e.g., the ability to repress Tsp-1) of Protease, Serine 2 (PRSS2) by inhibiting the binding of PRSS2 to LRP1. Further provided herein are control agents that bind to binding domain I of LRP1 and mimic the activity of prosaposin in stimulating Tsp-1 Methods of using these agents in treating cancer are also provided.