Circulating human interleukin-8 as an indicator of cancer progression in a nude rat orthotopic human non-small cell lung carcinoma model.
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; TCO(2), P = 0.024; pCO(2), P = 0.007; and HCO(3)(-), 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.
Millar
Hillary J
HJ
Discovery Research, Centocor R&D, Inc., Radnor, PA 19087, USA. hmillar@cntus.jnj.com
Nemeth
Jeffrey A
JA
McCabe
Francis L
FL
Pikounis
Bill
B
Wickstrom
Eric
E
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000097:blood*; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D016016:Proportional Hazards Models; D051381:Rats; D011923:Rats, Nude; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D014408:Biomarkers, Tumor; D016209:Interleukin-8; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9