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

Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
International Journal of Cancer (Impact Factor: 5.09). 12/2011; 129(12):2905-15. DOI: 10.1002/ijc.25942
Source: PubMed


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.

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Available from: Hop Sanderson Tran Cao
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    • "For example, α1β1, α2β1, α10β1 and α11β1 are collagen-binding integrins; α3β1, α6β1 and α7β1 bind to laminin and α4β1, α5β1, α8β1 and αvβ1 bind to fibronectin [30]. In many cancer types, integrin beta 1 promotes cancer cell proliferation and survival and regulates cell focal adhesion and tumor metastasis [31], [32], [33], [34]. Masumoto reported that a monoclonal antibody against ITGB1 blocked HCC cell invasion [35], and Mizuno found that overexpression of α3β1 integrins enhanced HepG2 cell migration and invasion [36], while inhibition of α3β1 integrins suppressed SMMC-7721 cell migration [37]. "
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    • "blocked cancer cell migration and invasion in vitro (Arao et al, 2000; Ryschich et al, 2009). In vivo, knockdown of b1 integrin reduced primary tumour growth by 50% and completely inhibited spontaneously occurring metastasis (Grzesiak et al, 2011). Consistently, our data provide additional insights to the combined blockage of integrin a2 and b1 subunits as a potential intervention in PDAC. "
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