Increased type IV collagenase in lgl-induced invasive tumors of Drosophila.
Loss of function mutations in the lethal giant larvae (lgl) gene causes neoplastic brain tumors in Drosophila. We have introduced a lacZ reporter gene into lgl mutant cells and used beta-galactosidase expression as a marker to monitor the growth of such tumors following transplantation into wild-type adult hosts. Whereas normal larval brains do not grow when transplanted, mutant brains can develop into enormous tumors that fill the entire abdominal cavity. To investigate whether these tumors are similar to mammalian tumors at the biochemical level, we examined 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 several metastatic human tumors. Using antibodies directed against this human 72 kDa type IV collagenase, we show for the first time that Drosophila has a cross-reacting 49 kDa protein with gelatinase activity. In brains 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 that 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.
Woodhouse
E
E
Biology Department, Johns Hopkins University, Baltimore, Maryland 21218.
Hersperger
E
E
Stetler-Stevenson
W G
WG
Liotta
L A
LA
Shearn
A
A
D000818:Animals; D001921:Brain / Q000201:enzymology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D017364:Collagenases / Q000032:analysis / Q000096:biosynthesis*; D003429:Cross Reactions; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D018093:Gelatinases / Q000032:analysis / Q000096:biosynthesis; D005804:Genes, Lethal; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis; D007814:Larva; D009154:Mutation; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation
D007527:Isoenzymes; D017364:Collagenases; D018093:Gelatinases