乳腺癌
CXCR3型
癌症研究
基因沉默
转移
淋巴结
肺癌
医学
癌症
病理
内科学
生物
免疫学
肿瘤科
趋化因子受体
受体
趋化因子
基因
生物化学
作者
Xinrong Ma,Kelly J. Norsworthy,Namita Kundu,William H. Rodgers,Phyllis A. Gimotty,Olga Goloubeva,Michael Lipsky,Yanchun Li,Dawn Holt,Amy M. Fulton
标识
DOI:10.1158/1535-7163.mct-08-0485
摘要
Abstract 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]
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