期刊
INTERNATIONAL JOURNAL OF CANCER
卷 129, 期 12, 页码 2905-2915出版社
WILEY
DOI: 10.1002/ijc.25942
关键词
integrins; extracellular matrix; pancreatic cancer; orthotopic mouse models; RNA interference
类别
资金
- NCI [R21CA135435]
- NIH [CA121938, DK00704]
- NHI [R01CA132971]
To address the role of beta(1) integrins in pancreatic cancer progression, we stably knocked down beta(1) integrin subunit expression in human FG-RFP pancreatic cancer cells using lentiviral-based RNA interference. We then examined the effects of beta(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 beta(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 beta(1) integrin subunit reduced primary tumor growth by 50% and completely inhibited spontaneously occurring metastasis. These observations indicate a critical role for the beta(1) integrin subunit in pancreatic cancer progression and metastasis in particular. Our results suggest the beta(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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