This study evaluated the relevance of CXCR2 chemokine receptors in oral squamous 
cell carcinoma, by means of in vitro and in vivo approaches. The in vitro 
incubation of the selective and non-peptide CXCR2 receptor antagonist 
N-(2-hydroxy-4-nitrophenyl)-N9-(2-bromophenyl) Urea (SB225002; 25 to 800 nM) 
produced a time- and concentration-dependent inhibition of SCC158 (rat) and HN30 
(human) cell lines viability. Conversely, this antagonist did not significantly 
affect the viability of the immortalized keratinocyte lineage, HaCaT. 
Additionally, the incubation of human IL-8 and rat CINC-1 CXCR2 agonists 
produced a concentration-related increase on HN30 and SCC158 proliferation. The 
submucosal injection of SCC158 cells (5 × 10(6) cells) into the tongue of 
Fischer 344 rats induced tumor development, which displayed typical clinical 
features. Immunohistochemical analysis of rat tongue biopsies revealed a marked 
increase of CXCR2 receptor immunoreactivity, which was accompanied by augumented 
expression of VEGF and caspase-3. Our data suggests an important role for CXCR2 
receptors in oral squamous cell carcinoma.