Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice.
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.
Arenberg
D A
DA
Department of Internal Medicine (Division of Pulmonary and Critical Medicine), University of Michigan Medical School, Ann Arbor 48109, USA.
Kunkel
S L
SL
Polverini
P J
PJ
Glass
M
M
Burdick
M D
MD
Strieter
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000517:prevention & control*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000502:physiology; D008175:Lung Neoplasms / Q000517:prevention & control*; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D016209:Interleukin-8