Compositions and Methods for Detecting Abnormal Cell Proliferation
Description of Invention:
The invention relates to the discovery that class 5 semaphorins are linked to cancer. A Drosophila model system was used to identify genes that functionally alter tumorigenicity or metastasis. 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 Semaphorin 5c (Sema 5c) as being required for tumorigenicity.
Semaphorin 5c, is a transmembrane protein with a large extracellular domain that contains seven thrombospondin type I (Tsp I) repeats. The semaphorin 5c gene belongs to the class 5 group of semaphorins, which are transmembrane proteins with short cytoplasmic (C-terminal) tails and extracellular domains containing seven thrombospondin type I repeats, a plexin domain, and a semaphorin domain sequences. Class 3 semaphorins, previously linked to cancer, are structurally different from class 5, lacking the thrombospondin repeats present in the transmembrane class 5 semaphorins.
The invention is a screening method using Drosophila to a) screen for functional important genes associated with cancer growth, invasion and metastasis, and b) screen for the effects of an anti-cancer targeted therapy by administering the therapy to the drosophila host bearing the tumor. In addition the invention covers a specific gene Semaphorin 5c which is a potential therapeutic target acting in the TGFbeta pathway.
As part of the invention, the inventors contemplate the following:
(i) a method of detecting an increased risk for abnormal cellular proliferation in a subject via detection of overexpression of the Sema 5 gene product;
(ii) methods and compositions for treating abnormal cellular proliferation in a subject by administering a molecule that decreases or prevents expression of a Sema 5 gene product or a molecule that binds to Sema 5 antigen on the surface of the cell and targets the cell for destruction.
Inventors:
Lance Liotta et al. (NCI)
Patent Status:
DHHS Reference No. E-253-2002/0 --
U.S. Provisional Application No. 60/466,154 filed 28 Apr 2003
U.S. Patent Application No. 10/835,531 filed 28 Apr 2004 Licensing Status: This technology is available for licensing on an exclusive or a non-exclusive basis.
Portfolios: Cancer
Cancer -Therapeutics-Immunoconjugates Cancer -Therapeutics-Gene Therapy Cancer -Diagnostics Cancer -Therapeutics
For Additional Information Please Contact: Jennifer Wong
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4633
Email: wongje@mail.nih.gov
Fax: (301)402-0220
