Inhibition of interleukin-8 Reduces Tumorigenesis of Human Non-Small Cell Lung Cancer in SCID Mice

J Clin Invest. 1996 Jun 15;97(12):2792-802. doi: 10.1172/JCI118734.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carcinoma, Non-Small-Cell Lung / prevention & control*
  • Female
  • Humans
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / physiology
  • Lung Neoplasms / prevention & control*
  • Mice
  • Mice, SCID
  • Molecular Sequence Data
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / prevention & control*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Interleukin-8