title: Knockdown of the β(1)  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.
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Grzesiak
authors.forename: Hop S
authors.initials: HS
authors.lastname: Tran Cao
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Burton
authors.forename: Sharmeela
authors.initials: S
authors.lastname: Kaushal
authors.forename: Fabian
authors.initials: F
authors.lastname: Vargas
authors.forename: Paul
authors.initials: P
authors.lastname: Clopton
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Snyder
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Deftos
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D016326:Extracellular Matrix Proteins; D019012:Integrin beta1