CXCR3 expression is associated with poor survival in breast cancer and promotes metastasis in a murine model
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- Xinrong Ma
- 1University of Maryland Greenebaum Cancer Center and
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- Kelly Norsworthy
- 1University of Maryland Greenebaum Cancer Center and
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- Namita Kundu
- 1University of Maryland Greenebaum Cancer Center and
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- William H. Rodgers
- 1University of Maryland Greenebaum Cancer Center and
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- Phyllis A. Gimotty
- 4Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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- Olga Goloubeva
- 1University of Maryland Greenebaum Cancer Center and
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- Michael Lipsky
- 2Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland;
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- Yanchun Li
- 1University of Maryland Greenebaum Cancer Center and
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- Dawn Holt
- 1University of Maryland Greenebaum Cancer Center and
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- Amy Fulton
- 1University of Maryland Greenebaum Cancer Center and
Description
<jats:title>Abstract</jats:title> <jats:p>Breast tumor cells express the chemokine receptor CXCR3, which binds the ligands CXCL9, CXCL10, and CXCL11. CXCR3 and other chemokine receptors may mediate tumor metastasis by supporting migration of tumor cells to sites of ligand expression including the lymph nodes, lungs, and bone marrow. We examined the relationship of CXCR3 expression to clinical outcome in 75 women diagnosed with early-stage breast cancer. We detected CXCR3 in malignant epithelium from all tumors. Twelve percent were weakly positive and 64% had moderate levels of CXCR3. Strong CXCR3-positive staining was observed in 24% of tumors. Kaplan-Meier survival curves showed that high CXCR3 expression was associated with poorer overall survival; the unadjusted hazard ratio was 1.56 and it was marginally significant (P = 0.07). When interactions between lymph node status and CXCR3 were considered, the adjusted hazard ratio for CXCR3 was 2.62 (P = 0.02) for women with node-negative disease at diagnosis, whereas the hazard ratio for CXCR3 was not significant for those with node-positive disease. CXCR3 gene silencing inhibited lung colonization and spontaneous lung metastasis from mammary gland–implanted tumors in a murine model. The size or growth rate of the locally growing tumors was not affected. The antimetastatic effect of CXCR3 gene silencing was compromised in mice depleted of Natural Killer cells or with mutations in IFN-γ, suggesting that the role of CXCR3 is not simply to mediate tumor cell trafficking. These studies support the continued examination of CXCR3 as a potential therapeutic target in patients with breast cancer. [Mol Cancer Ther 2009;8(3):490–8]</jats:p>
Journal
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- Molecular Cancer Therapeutics
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Molecular Cancer Therapeutics 8 (3), 490-498, 2009-03-01
American Association for Cancer Research (AACR)
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Details 詳細情報について
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- CRID
- 1361981470200175744
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- ISSN
- 15388514
- 15357163
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- Data Source
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- Crossref