Abstract
Since the NF-κB/relA transcription factor is constitutively activated in human prostate cancer cells, we determined whether blocking NF-κB/relA activity in human prostate cancer cells affected their angiogenesis, growth, and metastasis in an orthotopic nude mouse model. Highly metastatic PC-3M human prostate cancer cells were transfected with a mutated IκBα (IκBαM), which blocks NF-κB activity. Parental (PC-3M), control vector-transfected (PC-3M-Neo), and IκBαM-transfected (PC-3M-IκBαM) cells were injected into the prostate gland of nude mice. PC-3M and PC-3M-Neo cells produced rapidly growing tumors and regional lymph node metastasis, whereas PC-3M-IκBαM cells produced slow growing tumors with low metastatic potential. NF-κB signaling blockade significantly inhibited in vitro and in vivo expression of three major proangiogenic molecules, VEGF, IL-8, and MMP-9, and hence decreased neoplastic angiogenesis. Inhibition of NF-κB activity in PC-3M cells also resulted in the downregulation of MMP-9 mRNA and collagenase activity, resulting in decreased invasion through Matrigel. Collectively, these data suggest that blockade of NF-κB activity in PC-3M cells inhibits angiogenesis, invasion, and metastasis.
Original language | English (US) |
---|---|
Pages (from-to) | 4188-4197 |
Number of pages | 10 |
Journal | Oncogene |
Volume | 20 |
Issue number | 31 |
DOIs | |
State | Published - Jul 12 2001 |
Keywords
- Angiogenesis
- Invasion
- Metastasis
- NF-κB
- Prostate cancer
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research