INCREASED TYPE-IV COLLAGENASE IN IGI-INDUCED INVASIVE TUMORS OF DROSOPHILA

Loss of function mutations in the lethal giant larvae (lgl) gene cause s neoplastic brain tumors in Drosophila. We have introduced a lacZ rep orter gene into lgl mutant cells and used beta-galactosidase expressio n as a marker to monitor the growth of such tumors following transplan tation into wild-type adult hosts. Whereas normal larval brains do not grow when transplanted, mutant brains can develop into enormous tumor s that fill the entire abdominal cavity. To investigate whether these tumors are similar to mammalian tumors at the biochemical level, we ex amined the accumulation of a specific protein which is differentially expressed in mammalian metastatic tumors and is likely to be involved in the invasive and/or metastatic mechanism. Increased accumulation of a 72 kilodalton (kDa) type IV collagenase has been observed in severa l metastatic human tumors. Using antibodies directed against this huma n 72 kDa type IV collagenase, we show for the first time that Drosophi la has a cross-reacting 49 kDa protein with gelatinase activity. In br ains dissected from lgl mutant larvae, the accumulation of this 49 kDa gelatinase of Drosophila is increased compared to the level in brains dissected from wild-type larvae. In tumors derived from mutant brains , all of the cells express this protein. Moreover, the tumor cells tha t invade host organs express this protein. These data suggest that the metastasis of Drosophila tumor cells is similar to the metastasis of some human tumors at the biochemical level as well as at the cellular level.