Yanagie Hironobu, Hisa Tomoyuki, Ono Minoru, Eriguchi Masazumi
Dept. of Nuclear Engineering & Management, Graduate School of Engineering, The University of Tokyo, and Cooperative Unit of Medicine & Engineering, The University of Tokyo Hospital, Tokyo, Japan.
Gan To Kagaku Ryoho. 2010 Nov;37(11):2052-7.
The relationship has become clear between the expression of chemokine/chemokine receptors on cancer cells and the invasion, metastasis and peritoneal dissemination. Many cancer cells express chemokine receptors which are not expressed on the surface of normal tissues. Recently, it has been reported that overexpression of CXCR4/CXCL12 is related with metastasis to lung, liver, lymph nodes and bone marrow, while the overexpression of CCR7/CCL21 is mainly related with lymph node metastasis. We performed a comparative analysis of differential gene expressions related to chemokines/chemokine receptors, and cytokines in established gastric cancer cell lines by cDNA microarray. Upregulated chemokine genes were CCL21, CCL5, CXCL14, CCL2, CXCL1, CXCL8, CXCL7 and CXCL12, which the downregulated chemokines genes were MIP-1alpha and TECK. The upregulated gene of chemokine receptors was CCR-6. In the cancer microenvironment, cancer cells readily formed edematous and inflammatory conditions, easily metastasizing to other organs with the suppression of dendritic cells. The chemokines/chemokine receptors will hopefully become the new targets for cancer therapies for the regulation of metastasis.
癌细胞上趋化因子/趋化因子受体的表达与侵袭、转移及腹膜播散之间的关系已变得清晰。许多癌细胞表达正常组织表面未表达的趋化因子受体。最近，有报道称CXCR4/CXCL12的过表达与肺、肝、淋巴结及骨髓转移相关，而CCR7/CCL21的过表达主要与淋巴结转移相关。我们通过cDNA微阵列对已建立的胃癌细胞系中与趋化因子/趋化因子受体及细胞因子相关的差异基因表达进行了比较分析。上调的趋化因子基因有CCL21、CCL5、CXCL14、CCL2、CXCL1、CXCL8、CXCL7和CXCL12，下调的趋化因子基因有MIP-1α和TECK。趋化因子受体上调的基因是CCR-6。在癌症微环境中，癌细胞容易形成水肿和炎症状态，在树突状细胞受抑制的情况下容易转移至其他器官。趋化因子/趋化因子受体有望成为调控转移的癌症治疗新靶点。
