| Summary: | 碩士 === 中國醫藥大學 === 臨床醫學研究所碩士班 === 99 === Lung cancer is the most commonly diagnosed malignancy and the leading cause of cancer-related deaths in Western and Asian populations. Local invasion and distant metastasis usually develop at initial diagnosis. Certain chemokine receptors have been identified on tumor cells in several malignancies, including breast and lung cancers, and chemokine-induced signaling increases proliferation and pro-metastatic functions of cancer cells. CXCR7 is a new chemokine receptor that involves in several biological and pathological processes, including cell proliferation and adhesion. CXCR7 promotes breast and colon cancer growth through expression in malignant cells and may regulate carcinogenesis in a variety of common malignancies. Overexpression of CXCR7 has also been observed in various tumors, including breast, lung, prostate and pancreatic cancers. However, there is little information about the role of CXCR7 expression in clinical metastasis of human lung cancer and the mediation of action is still not clear.
Purpose:
To investigate the relationship between CXCR7 expression and the presence of metastasis in non-small cell lung cancer (NSCLC) patients and to evaluate the role of CXCR7 expression on the metastatic potential of NSCLC cells.
Experimental Designs:
CXCR7 expression in surgical specimens of 48 NSCLC patients was detected by immunohistochemistry and the relationship between CXCR7, clinical metastasis and survival was analyzed. In vitro, CXCR7 expression in two human lung adenocarcinoma cell lines (CL1-5 and CL1-0) was evaluated and modulated by transfection with the plasmid DNA containing CXCR7 coding gene or CXCR7 antisense nucleotide fragment. The effects of CXCR7 modulation on migration, invasion, proliferation, MMP-9 production and activity of lung cancer cells were measured.
Results:
Expression of CXCR7 was identified in 47 tumors, which were further divided into 32 high expression and 15 low expression tumors by their staining intensities. In comparison with low CXCR7-expression tumors, high CXCR7-expression tumors (19 of 32) were significantly prone to develop clinical metastasis. In vitro, modulation of CXCR7 expression significantly altered the metastatic potential, including migration, invasion, proliferation, MMP-9 production and activity, of lung cancer cells.
Conclusions:
Chemokine receptor CXCR7 is expressed and associated with the metastatic potential of human NSCLC by the mediation of MMP-9. CXCR7 expression might be one of the prognositc factors and therapeutic targets of NSCLC patients.
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