Fully human anti-interleukin 8 antibody inhibits tumor growth in orthotopic bladder cancer xenografts via down-regulation of matrix metalloproteases and nuclear factor-kappaB.
| Autor: | Mian BM; Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA., Dinney CP, Bermejo CE, Sweeney P, Tellez C, Yang XD, Gudas JM, McConkey DJ, Bar-Eli M |
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| Jazyk: | angličtina |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2003 Aug 01; Vol. 9 (8), pp. 3167-75. |
| Abstrakt: | Purpose: We previously demonstrated that overexpression of interleukin 8 (IL-8) in human transitional cell carcinoma (TCC) resulted in increased tumorigenicity and metastasis. This increase in tumor growth and metastasis can be attributed to the up-regulation in the expression and activity of the metalloproteinases MMP-2 and MMP-9. Experimental Design: To investigate whether targeting IL-8 with a fully human anti-IL-8 antibody (ABX-IL8) could be a potential therapeutic strategy for controlling TCC growth, we studied its effects on TCC growth in vitro and in an in vivo mouse model. Human TCC cell lines 253J B-V and UM UC3 (high IL-8 producers), 253J (low IL-8), and 253J transfected with the IL-8 gene (high producer) were used. Results: ABX-IL8 had no effect on TCC cell proliferation in vitro. However, in the orthotopic nude mouse model, after 4 weeks of treatment (100 micro g/week, i.p.), a significant decrease in tumor growth of both cell lines was observed. IL-8 blockade by ABX-IL8 significantly inhibited the expression, activity, and transcription of MMP-2 and MMP-9, resulting in decreased invasion through reconstituted basement membrane in vitro. The down-regulation of MMP-2 and MMP-9 in these cells could be explained by the modulation of nuclear factor-kappaB expression and transcriptional activity by ABX-IL8. Conclusions: Our data point to the potential use of ABX-IL8 as a modality to treat bladder cancer and other solid tumors, either alone or in combination with conventional chemotherapy or other antitumor agents. |
| Databáze: | MEDLINE |
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