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Circulating Human Interleukin-8 as an Indicator of Cancer Progression in a Nude Rat Orthotopic Human Non–Small Cell Lung Carcinoma Model

¹ Discovery Research, Centocor R&D, Inc., Radnor, Pennsylvania; ² Nonclinical Statistics, Centocor R&D, Inc., Malvern, Pennsylvania; and ³ Department of Biochemistry and Molecular Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania

Requests for reprints: Hillary J. Millar, Discovery Research, Centocor R&D, Inc., Radnor, PA 19087. Phone: 610-240-8727; Fax: 610-651-6152. E-mail: hmillar{at}cntus.jnj.com

Clinically relevant animal models of human cancer are necessary for the evaluation of putative therapeutics. We hypothesized that circulating human lung cancer–associated proteins would correlate with physiologic measurements from an orthotopic H460 human non–small cell lung carcinoma model that we developed in immunodeficient rats. Physiologic measurements and serum samples were collected over time. Serum interleukin-8 (IL-8), p53, vascular endothelial growth factor, and matrix metalloproteinase-9 were quantitated for correlation with physiologic measurements. Matrix metalloproteinase-9 and p53 were not significantly detectable. Circulating vascular endothelial growth factor was detected at high levels in some tumor-bearing animals. Human IL-8 was detectable in all tumor-bearing animals and correlated positively with markers of respiratory acidosis (pH, P = 0.012; TCO₂, P = 0.024; pCO₂, P = 0.007; and HCO₃^–, P = 0.029) and with surface body temperature (P = 0.001) beginning on day 16 after implantation. IL-8 levels negatively correlated with survival (P < 0.001), indicating an association with tumor burden. Circulating human IL-8 might be a useful, clinically relevant circulating tumor protein marker due to its positive correlation with multiple physiologic variables associated with lung cancer progression. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2180–7)