Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice. (original) (raw)

Research Article Free access | 10.1172/JCI118734

S L Kunkel, P J Polverini, M Glass, M D Burdick, and R M Strieter

Department of Internal Medicine (Division of Pulmonary and Critical Medicine), University of Michigan Medical School, Ann Arbor 48109, USA.

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Department of Internal Medicine (Division of Pulmonary and Critical Medicine), University of Michigan Medical School, Ann Arbor 48109, USA.

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Department of Internal Medicine (Division of Pulmonary and Critical Medicine), University of Michigan Medical School, Ann Arbor 48109, USA.

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Department of Internal Medicine (Division of Pulmonary and Critical Medicine), University of Michigan Medical School, Ann Arbor 48109, USA.

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Department of Internal Medicine (Division of Pulmonary and Critical Medicine), University of Michigan Medical School, Ann Arbor 48109, USA.

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Department of Internal Medicine (Division of Pulmonary and Critical Medicine), University of Michigan Medical School, Ann Arbor 48109, USA.

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Published June 15, 1996 -More info

Published June 15, 1996 -Version history

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Abstract

The salient feature of solid tumor growth is the strict dependence on local angiogenesis. We have previously demonstrated that IL-8 is an angiogenic factor present in freshly isolated specimens of human non-small cell lung cancer (NSCLC). Using a model of human NSCLC tumorigenesis in SCID mice, we now report that IL-8 acts as a promoter of human NSCLC tumor growth through its angiogenic properties. Passive immunization with neutralizing antibodies to IL-8 resulted in more than 40% reduction in tumor size and was associated with a decline in tumor-associated vascular density and angiogenic activity. IL-8 did not act as an autocrine growth factor for NSCLC proliferation. The reduction in primary tumor size in response to neutralizing antibodies to IL-8 was also accompanied by a trend toward a decrease in spontaneous metastasis to the lung. These data support the notion that IL-8 plays a significant role in mediating angiogenic activity during tumorigenesis of human NSCLC, thereby offering a potential target for immunotherapy against solid tumors.

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