NEW YORK (Reuters Health) - Upregulation of the CXC chemokine receptor 4 (CXCR4) appears essential for human epithelial growth factor 2 (HER2)-mediated breast cancer metastasis, researchers report in the November issue of Cancer Cell.
Why HER2-positive cancer cells preferentially travel to organs such as the lung, liver and bones has “always been a puzzle,” senior author Dr. Mien-Chie Hung said in a statement. “We have now explained it biochemically, and hope this leads to strategies that prevent such metastasis.”
Dr. Hung of M.D. Anderson Cancer Center, Houston, and colleagues established that CXCR4 plays an important role in HER2-mediated metastasis. They found that CXCR4 expression was 2.8 times greater in HER2 transfectants of certain breast cancer cells than in vector control cells.
Moreover, use of a monoclonal antibody that downregulated HER2 expression led to downregulation of CXCR4. Similar results were seen when RNA interference was used to deplete HER2 expression.
Metastasis, say the investigators, appears to be mediated by stromal cell-derived factor-1a (SDF-1a), which is produced by target organs. SDF1a sends homing signals to the CXCR4 receptors on the HER2 cancer cells.
Thus, “HER2 turns on and then magnifies the ability of these cancer cells to zero in on organs that release this chemical signal,” Dr. Hung continued.
“CXCR4 expression is correlated with overall patient survival in breast cancer,” the researchers report. Therefore, they conclude that the findings “will have important clinical implications.”
Source: Cancer Cell 2004;6:459-469. [ Google search on this article ]
MeSH Headings:Immunologic and Biological Factors: Immunologic Factors: Membrane Proteins: Receptors, Cell Surface: Receptors, Immunologic: Receptors, Virus: Receptors, HIV: Receptors, Cytokine: Genes, erbB-2: Genes, erbB: Receptors, Chemokine: Receptors, CXCR4: Chemical Actions and Uses: Chemical Actions: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
