first there was Tiptoe, now there is Dachsund!!
 

: Proc Natl Acad Sci U S A. 2008 May 8 [Epub ahead of print]

Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8.

Wu K, Katiyar S, Li A, Liu M, Ju X, Popov VM, Jiao X, Lisanti MP, Casola A, Pestell RG.
Departments of Cancer Biology and.
Oncogene-mediated signaling to the host environment induces a subset of cytokines and chemokines. The Drosophila Dac gene promotes migration of the morphogenetic furrow during eye development. Expression of the cell-fate determination factor Dachshund (DACH1) was lost in poor prognosis invasive breast cancer. Mouse embryo fibroblasts derived from Dach1(-/-) mice demonstrated endogenous Dach1 constitutively represses cellular migration. DACH1 inhibited cellular migration and invasion of oncogene (Ras, Myc, ErbB2, c-Raf)-transformed human breast epithelial cells. An unbiased proteomic analysis identified and immunoneutralizing antibody and reconstitution experiments demonstrated IL-8 is a critical target of DACH1 mediating breast cancer cellular migration and metastasis in vivo. DACH1 bound the endogenous IL-8 promoter in ChIP assays and repressed the IL-8 promoter through the AP-1 and NF-kappaB binding sites. Collectively, our data identify a pathway by which an endogenous cell-fate determination factor blocks oncogene-dependent tumor metastasis via a key heterotypic mediator.

HUH? I must have had too much wine tonight with the ribs.
But on second reading I am NOT seeing things.
Still don't quite understand ....

Interleukin 8 is one of many cyokines. apparently it is necessary or involved in the metastasis of breast cancer cells. apparently this Dasch gene protein inhibits metastasis by inhibiting the action of interleukin 8 when it is functioning properly.

It would be quite possible to develop a monoclonal antibody to inhibit interleukin 8 and help slow down metastasis. Avastin is a monoclonal antibody that inhibits Vascular Endothelial Growth Factor. Herceptin is a monoclonal antibody that in hibits the Her2Neu protein. Tocilizumab is a monoclonal antibody being developed against Interleukin 6 and is to be used to treat severe Rheumatoid Arthritis.Interleukin 6 is very involved in the cancer known as Multiple Myeloma so theoretically Tocilizumab might be valable in this disease too.

This new info about Dasch and Interlekin 8 opens p a new area to target. NF Kappa beta is also mentioned. Stimulation of NFKappa beta causes Interleukin 6 release and apparently the Dasch gene also inhibits this target also. In fact when NFKappa b is activated a large number of "pro-cancer" (for lack of a better word) chemicals are activated. I know as a pharmacist that NSAID drgs like Aspirin and Celebrex inhibit NFKappa b also and could be used in combination with this antibody against Interleukin 8, when it is developed.

Paul

And excess Omega six promotes higher levels of IL6.

RB

Better NOT tell my daughter or my niece sinch they both have long-haired mini Dachs...
Close your long floppy ears Tootsie and Miloo.

Thanks for the lay-speak.
I heard about dozens of new targets being worked on when we were at San Diego, so this actually does not surprise me that much.

Lucky for my 9 week old...
 

miniature short hair dashchund that HE is a boy...WHEW, lucky Oscar.

Rhonda

Wish I had known - as we had over 500 wiener-dogs competing at the world famous Buda, Texas Wiener Dog Races last weekend (2 blocks from my house)... I coulda done some "harvesting" LOL.