Knockdown of the β₁ integrin subunit reduces primary tumor growth and inhibits pancreatic cancer metastasis

Abstract

To address the role of β(1) integrins in pancreatic cancer progression, we stably knocked down β(1) integrin subunit expression in human FG-RFP pancreatic cancer cells using lentiviral-based RNA interference. We then examined the effects of β(1) integrin subunit knockdown on pancreatic cancer cell adhesion, migration and proliferation on tumor microenvironment-specific extracellular matrix proteins in vitro and on tumor progression in vivo using a clinically relevant fluorescent orthotopic mouse model of pancreatic cancer. Knockdown of the β(1) integrin subunit inhibited cell adhesion, migration and proliferation on types I and IV collagen, fibronectin and laminin in vitro. In vivo, knockdown of the β(1) integrin subunit reduced primary tumor growth by 50% and completely inhibited spontaneously occurring metastasis. These observations indicate a critical role for the β(1) integrin subunit in pancreatic cancer progression and metastasis in particular. Our results suggest the β(1) integrin subunit as a therapeutic target for the treatment of pancreatic cancer, especially in the adjuvant setting to prevent metastasis of this highly aggressive cancer.