Science

CXCR4 tied to breast cancer metastasis

Last Updated: 2004-11-29 14:41:55 -0400 (Reuters Health)

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."

Cancer Cell 2004;6:459-469.