Mechanisms linking inflammation and cancer

摘要

Adhesion of neutrophils (PMNs) to the endothelium facilitates melanoma cell extravasation by binding of intercellular adhesion molecule-1 (ICAM-1) on melanoma cells to ? integrins on PMNs, which is mediated by endogenously produced interleukin 8 (IL-8) from the tumor microenvironment. B-Raf is the most mutated gene in melanomas. Present study has indicated that knockdown of mutant V600EB-Raf inhibits melanoma cell extravasation in vitro and subsequent lung metastasis development in vitro. Mechanistically, inhibition of mutant V600EB-Raf reduces melanoma extravasation by inhibiting downstream NF-?B mediated endogenous IL-8 production and ICAM-1 expressions in melanoma cells. This work provides potential anti-inflammatory therapeutics for targeting mutant V600EB-Raf to inhibit melanoma extravasation and subsequent metastasis development.