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 an giogenic factor present in freshly isolated specimens of human non-sma ll cell lung cancer (NSCLC). Using a model of human NSCLC tumorigenesi s In SCID mice, Ne now report that IL-8 acts as a promoter of human NS CLC tumor growth through its angiogenic properties. Passive immunizati on with neutralizing antibodies to IL-8 resulted in more than 40% redu ction in tumor size and was associated with a decline in tumor-associa ted vascular density and angiogenic activity. IL-8 did not act as an a utocrine growth factor for NSCLC proliferation. The reduction in prima ry 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 NS CLC, thereby offering a potential target for immunotherapy against sol id tumors.