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.