PREVENTION OF TUMOR-GROWTH AND METASTASIS BY INTERLEUKIN (IL)-10 TRANSFECTION - A POTENT INHIBITORY ROLE OF IL-10 ON ANGIOGENESIS

The influence of interleukin-10 (IL-10) on tumor growth and metastasis was evaluated in murine melanoma and sarcoma cells manipulated by gen e transfer to secrete IL-10. IL-10 gene transfection of the tumor cell s resulted in antimetastatic and antitumor effects, which correlated w ith the amount of IL-10 secretion; mice given injection of the highest IL-10-secretors developed neither subcutaneous growth nor pulmonary m etastasis. This effect of IL-10 transfection was inhibited by anti-IL- 10 antibodies. In addition, IL-10-secreting cells suppressed the subcu taneous growth of coinjected parental tumor cells. Immunohistology wit h anti-CD68 and anti-CD34 antibodies revealed that macrophage infiltra tion and neovasculization within parental sarcoma tumors were profound ly inhibited in IL-10-transfected tumors. These findings strongly sugg est that IL-10 suppresses the tumor growth by inhibiting the formation of new blood vessels within the tumors, the formation of which is ach ieved by tumor infiltrating macrophages.