Metastatic ability of Drosophila tumors depends on MMP activity.
We analyzed how cells from tumors caused by mutations in either lgl or brat use matrix metalloproteinases (MMPs) to facilitate metastasis in Drosophila. MMP1 accumulation is dramatically increased in lgl larval imaginal discs compared to both wild type and brat mutants. Removal of Mmp1 gene activity in lgl brain tumor cells reduced their frequency of ovarian micro-metastases after transplantation; whereas, removal of Mmp1 gene activity in brat tumor cells had no such effect. Host ovaries showed increased Mmp1 gene expression in response to transplantation of brat tumors but not of lgl tumors. Reduction of MMP activity in host ovaries by ectopic expression of TIMP significantly reduced both lgl and brat metastases in that organ. These results highlight the mechanisms that lgl and brat tumor cells use to metastasize. Our interpretation of these data is that secretion of MMP1 from lgl tumor cells facilitates their metastasis, while secretion of MMP1 from host ovaries facilitates brat tumor metastasis. This study is the first demonstration that Drosophila tumors utilize MMP activity to metastasize.
Beaucher
Michelle
M
Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
Hersperger
Evelyn
E
Page-McCaw
Andrea
A
Shearn
Allen
A
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001921:Brain / Q000002:abnormalities / Q000254:growth & development; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017344:Genes, Insect; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics / Q000556:secondary*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins; C412783:brat protein, Drosophila; C081435:l(2)gl protein, Drosophila; D020781:Matrix Metalloproteinase 1