NF-κB activity blockade impairs the angiogenic potential of human pancreatic cancer cells
The effect of blockade of NF-κB activity on human pancreatic cancer angiogenesis was determined in an orthotopic xenograft model. Highly metastatic L3.3 human pancreatic cancer cells, which expressed an elevated level of constitutive NF-κB activity, were transfected with a mutated IκBα (IκBαM). After implantation in the pancreas of nude mice, parental (L3.3) and control vector-transfected (L3.3-Neo) cells produced rapidly growing tumors and liver metastases, whereas IκBαM-transfected (L3.3-IκBαM) cells had decreased tumorigenicity and metastatic potential. NF-κB signaling blockade significantly inhibited the in vitro and in vivo expression of the major proangiogenic molecules vascular endothelial growth factor and interleukin-8 and decreased tumor vascular formation. These events were correlated with retarded tumor growth and suppression of metastasis. Collectively, these data suggest that suppression of tumorigenicity and metastasis by NF-κB blockade is due to impaired angiogenic potential of tumor cells. © 2003 Wiley-Liss, Inc.
Xiong, HQ; Abbruzzese, JL; Lin, E; Wang, L; Zheng, L; Xie, K
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