Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis.

[RhondaH]

Ok, now we know what CAUSES the metastatis, now what to prevent it.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15542430&dopt=Abstract

More info on CXCR4
http://en.wikipedia.org/wiki/CXCR4

Rhonda

[jhandley]

Hi rhonda

I found this reference on CXCR4. I was particularly interested in the sentences I have highlighted. If this MAb turns off CXCR4 then it might stop her 2 mets as well as HIV.



Food for thought.

Jackie

FUSIN ANTISERA

Background:Fusin (CXCR4) (subject to patent by University of Pa) is a seven-transmembrane domain G-protein linked chemokine receptor. It has the highest degree of sequence homology with IL-8 receptors. Fusin is expressed on a wide variety of CD4+ and CD4- cells including those from spleen, brain and lung. The gene is located on chromosome 2 close to other chemokine receptor genes. The CXC chemokine, stromal cell-derived factor-1 (SDF-1), was recently identified as the ligand for Fusin . This molecule is strongly chemotactic for monocytes and lymphocytes. Messenger RNA for SDF-1 has been detected in a wide range of tissues and it has been suggested that it may have a role in immune surveillance or lymphocyte recirculation, rather than in inflammation. SDF-1 is highly conserved in human and mouse and studies on SDF-1 knockout mice reveal an essential function in development, as the mice show defects in B cell lymphopoiesis, bone marrow myelopoiesis and in the structure of the heart.
Fusin functions as a cofactor for infection with T-cell tropic strains of HIV-1. Immunoprecipitation of Fusin with the HIVgp120-CD4 complex suggests a direct mode of action for Fusin as a co-receptor. The monoclonal antibody (mAb), 12G5, is specific for Fusin. Some HIV-2 isolates can utilize Fusin as a receptor for CD4-independent infection. 12G5 blocks both CD4-independent infection by HIV-2, and CD4-dependent infection by certain T-cell tropic isolates of HIV-11-5 and does not cross-react with IL8RA (CXCR1), IL8RB (CXCR2), CCR1, CCR2, CCR3, CCR4 or CCR5 (http://www.researchd.com/cytokines/ccr5ab.htm) or the murine SDF-1 receptor.

REFERENCES

1. Loetscher, M., T. Geiser, T. O'Reilly, et al. 1994. Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J. Biol. Chem. 269: 232.


2. Simmons, G., D. Wilkinson, J.D. Reeves, et al. 1996. Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry. J. Virol. 70: 8355.


3. Nagasawa, T., T. Nakajima, K. Tachibana, et al. 1996. Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 receptor, a murine homolog of the human immunodeficiency virus 1 entry coreceptor fusin. Proc. Natl. Acad. Sci. USA 93: 14726.


4. Endres, M.J., P.R. Clapham, M. Marsh, et al. 1996. CD4-independent infection by HIV-2 is mediated by fusin/CXCR4. Cell 87: 745.
5. Feng, Y., C.C. Broder, P.E. Kennedy, et al. 1996. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G-protein-coupled receptor. Science 272:809.