Drosophila brain tumor metastases express both neuronal and glial cell type markers

Abstract

Loss of either lgl or brat gene activity in Drosophila larvae causes neoplastic brain tumors. Fragments of tumorous brains from either mutant transplanted into adult hosts over-proliferate, and kill their hosts within 2 weeks. We developed an in vivo assay for the metastatic potential of tumor cells by quantifying micrometastasis formation within the ovarioles of adult hosts after transplantation and determined that specific metastatic properties of lgl and brat tumor cells are different. We detected micrometastases in 15.8% of ovarioles from wild type host females 12 days after transplanting lgl tumor cells into their abdominal cavities. This frequency increased significantly with increased proliferation time. We detected micrometastases in 15% of ovarioles from wild type host females 10 days after transplanting brat tumor cells into their abdominal cavities. By contrast, this frequency did not change significantly with increased proliferation time. We found that nearly all lgl micrometastases co-express the neuronal cell marker, ELAV, and the glial cell marker, REPO. These markers are not co-expressed in normal brain cells nor in tumorous brain cells. This indicates deregulated gene expression in these metastatic cells. By contrast, most of the brat micrometastases expressed neither marker. While mutations in both lgl and brat cause neoplastic brain tumors, our results reveal that metastatic cells arising from these tumors have quite different properties. These data may have important implications for the treatment of tumor metastasis.

Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system

“…In addition to affecting the number of neurons and glia, altering the interconnected loops generates stable intermediate neuronal/glial fates, a phenotype that was observed in metastatic brain tumours 43 , implying that ambiguous fates may represent a signature of cancer cells. Interestingly, the intermediate phenotype occurs transiently in natural conditions in the neuronal progeny issued from the neuroGPs.…”

Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module

“…In this process, genetic interactions between a weak lgl mutant combination and dlg or scrib mutants have been described (Zhao et al, 2008). Furthermore, transplantation studies of lgl or dlg mutant imaginal disc epithelial or brain tumours into wild-type adult hosts have shown how tumour cells can continue to proliferate and metastasize, degrading basement membranes and penetrating muscle layers to infiltrate the host ovary (Woodhouse et al, 1994(Woodhouse et al, , 1998Caussinus and Gonzalez, 2005;Beaucher et al, 2006Beaucher et al, , 2007. The effects of scrib mutant tissues in invasion/metastasis have not been as well characterized as dlg or lgl mutant tissues.…”

The cell survival pathways of the primordial RNA-DNA complex remain conserved in the extant genomes and may function as proto-oncogenes

“…Ancient retroviral inserts express Sp1-binding sites (species-specifi c gene expression stimulatory proteins binding to GC box GGGCGGG motifs). In the drosophila genome, proto-oncogene expressions are intensifi ed by Sp1-stimulated retroviral inserts [90][91][92]. In general, ancient retroviral inserts are activators of protooncogenes [1,93].…”