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  • Knockdown of the β(1) integrin subunit reduces primary tumor growth and inhibits pancreatic cancer metastasis.

Knockdown of the β(1) integrin subunit reduces primary tumor growth and inhibits pancreatic cancer metastasis.

International journal of cancer (2011-04-15)
John J Grzesiak, Hop S Tran Cao, Douglas W Burton, Sharmeela Kaushal, Fabian Vargas, Paul Clopton, Cynthia S Snyder, Leonard J Deftos, Robert M Hoffman, Michael Bouvet
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Integrin α4 Antibody, clone P1H4, clone P1H4, Chemicon®, from mouse
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Anti-Integrin β1 Antibody, clone P5D2, clone P5D2, Chemicon®, from mouse
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Anti-Integrin α1 Antibody, clone FB12, clone FB12, Chemicon®, from mouse
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Anti-Integrin β6 Antibody, clone R6G9, azide free, clone R6G9, Chemicon®, from mouse
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Anti-Integrin αVβ5 Antibody, clone P1F6, clone P1F6, Chemicon®, from mouse
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Anti-Integrin αVβ3 Antibody, clone LM609, clone LM609, Chemicon®, from mouse
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Anti-Integrin αVβ6 Antibody, clone 10D5, azide free, clone 10D5, Chemicon®, from mouse
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Anti-Integrin β4 Antibody, clone ASC-3, clone ASC-3, Chemicon®, from mouse
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Anti-Integrin α2 Antibody, clone P1E6, clone P1E6, Chemicon®, from mouse
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Anti-Integrin α6 Antibody, clone NKI-GoH3, clone NKI-GoH3, Chemicon®, from rat