Reuters Health Information (2004-11-29): CXCR4 tied to breast cancer metastasis
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
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
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
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
"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.