Drosophila genetics can be a screening model for metastasis.

2003 DEC 2 - (NewsRx.com & NewsRx.net) -- Drosophila genetics can be a screening model for metastasis.

"Cancer metastasis is a complex process involving many genes and pathways. This complexity hinders the identification of molecules functionally required for this process. We have developed and used a Drosophila screening system to identify genes that are functionally important for tumorigenicity and metastasis," scientists in the United States report.

"Deletion of Drosophila lethal giant larvae (l(2)gl) leads to highly invasive and widely metastatic tumors on transplantation into adult flies. Random homozygous P element insertions were screened for the ability to modulate the l(2)gl phenotype. Analysis of metastasis patterns of the lines containing P element insertions and lacking wild-type l(2)gl expression identified three homozygous mutations that dramatically alter tumorigenesis and/or metastasis," wrote E.C. Woodhouse and colleagues, National Cancer Institute, Pathology Laboratory.

"Semaphorin Sc (Sema 5c) is required for tumorigenicity, apontic overexpression suppresses metastasis but not tumorigenicity, and pointed up-regulation accelerates lethality of l(2)gl tumors. Furthermore, class 5 semaphorins are shown to be expressed in cancer cells and localized to the membrane," the researchers wrote.

"Drosophila Sema-5c and the mammalian homologs are transmembrane proteins with extracellular thrombospondin type I (Tspl) repeats. Tspl repeats are known in some proteins to bind and activate transforming growth factor (TGF)-beta ligand. Phospho-Mad and the downstream target gene vestigial were elevated in l(2)gl tumors, thus linking Drosophila neoplasia to the Dpp (TGF-beta-like) signal pathway," the researchers stated.

The researchers concluded: "The activation of the Dpp pathway in 1(2)gl tumors occurred only in the presence of Sema-5c. This study demonstrates that the power of Drosophila genetics can be applied to screen, identify, and characterize molecules that are functionally required for invasion and metastasis."

Woodhouse and colleagues published their study in the Proceedings of the National Academy of Sciences USA (Drosophila screening model for metastasis: Semaphorin 5c is required for I(2)gl cancer phenotype. Proc Natl Acad Sci USA, 2003;100(20):11463-11468).

For more information, contact L.A. Liotta, National Cancer Institute, Pathology Laboratory, Center Cancer Research, National Institutes of Health, Bldg. 10, Room 2A33, 9000 Rockville Pike, Bethesda, MD 20892 USA.

Publisher contact information for the journal Proceedings of the National Academy of Sciences USA is: The National Academy of Sciences, 2101 Constitution Avenue NW, Washington, DC 20418 USA.

The information in this article comes under the major subject areas of Oncology.

This article was prepared by Cancer Weekly editors from staff and other reports.