Guo Zhigang, Cai Shaoxi, Fang Rui, Chen Hongyuan, Du Jun, Tan Yi, Ma Weifeng, Hu Houwen, Cai Shaohui, Liu Yiyao
College of Bioengineering, Key Laboratory for Biomechanics and Tissue Engineering of the State Ministry of Education, Chongqing University, Chongqing 400044, PR China.
Colloids Surf B Biointerfaces. 2007 Oct 15;60(1):1-6. doi: 10.1016/j.colsurfb.2007.05.013. Epub 2007 May 25.
CXC chemokine receptor 4 (CXCR4) is a cell surface receptor that has been reported to mediate the metastasis of many solid tumors including ovarian, breast, lung and prostate. The over-expression of the epidermal growth factor receptor (EGFR) is associated with the majority of ovarian cancer and has been implicated in the process of malignant transformation by promoting cell proliferation, survival, and motility. In this research, the result first showed that epidermis growth factor (EGF) enhanced the expression of CXCR4 and the migration of ovarian cancer cells, moreover, both stromal cell derived factor-1alpha (SDF-1alpha) and EGF-induced high matrix metallopeptidase 9 (MMP9) expressions. Molecular analysis indicated that augmented CXCR4 and MMP9 expression was regulated by phosphatidylinositol-3-kinase(PI3K)/Akt signal transduction pathway. These results suggested a possible important "cross-talk" between CXCR4 and EGFR intracellular pathways that might link signals of tumor deteriorated and provided a plausible explanation for the poor overall survival rate of patients whose co-expression of CXCR4 and EGFR was detected in their tissue sections. It enlightened that, compared to the respective inhibition of the EGFR or CXCR4 signaling, the simultaneous inhibition of them might be a more useful therapeutic strategy of cancer.
CXC趋化因子受体4（CXCR4）是一种细胞表面受体，据报道它可介导包括卵巢癌、乳腺癌、肺癌和前列腺癌在内的多种实体瘤的转移。表皮生长因子受体（EGFR）的过度表达与大多数卵巢癌相关，并通过促进细胞增殖、存活和运动性参与恶性转化过程。在本研究中，结果首先表明表皮生长因子（EGF）增强了CXCR4的表达以及卵巢癌细胞的迁移，此外，基质细胞衍生因子-1α（SDF-1α）和EGF均诱导了高基质金属蛋白酶9（MMP9）的表达。分子分析表明，CXCR4和MMP9表达的增加受磷脂酰肌醇-3-激酶（PI3K）/Akt信号转导通路调控。这些结果提示CXCR4和EGFR细胞内途径之间可能存在重要的“串扰”，这可能将肿瘤恶化信号联系起来，并为在组织切片中检测到CXCR4和EGFR共表达的患者总体生存率较低提供了合理的解释。这启示我们，与单独抑制EGFR或CXCR4信号相比，同时抑制它们可能是一种更有效的癌症治疗策略。
