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最近,Warner等人用试验证明了内皮细胞通过由CXC趋化因子信号介导的交联对话增强肿瘤细胞的侵袭。所有的假设是建立在内皮细胞通过分泌趋化因子并为肿瘤细胞产生趋化性梯度来积极参与肿瘤细胞侵袭这一基础上的。试验证明,同与空白的载体对照(HDMEC-LXSN)共同培养相比,与稳定表达Bcl-2的人类皮肤毛细血管内皮细胞(HDMEC-Bcl-2)共同培养时,口腔鳞状细胞癌-3(OSCC3)和卡波西(氏)肉瘤(SLK)表现出侵袭力增强。同作为对照的HDMEC-LXSN血管化的OSCC3肿瘤相比,HDMEC-Bcl-2血管化的OSCC3肿瘤呈现出更高的局部侵袭力。在暴露于血管内皮生长因子(VEGF)的初级内皮细胞和HDMEC-Bcl-2中,CXCL1和CXCL8均起正调节作用。值得注意的是,阻碍CXCR2的信号传导而不阻碍CXCR1的信号传导,使得OSCC3和SLK向内皮细胞的侵袭受到抑制。这些资料证明内皮细胞分泌的CXC趋化因子诱导肿瘤细胞的侵袭,而且内皮细胞产生的趋化信号引导了区域性癌变中观察到的肿瘤细胞的向外扩散过程。
Recently, Warner et al. Demonstrated with experiments that endothelial cells enhance tumor cell invasion through cross-talk mediated by CXC chemokine signaling. All hypotheses are based on the active involvement of endothelial cells in tumor cell invasion by the secretion of chemokines and the production of chemotactic gradients in tumor cells. Experiments demonstrated that, when co-cultured with human skin capillary endothelial cells stably expressing Bcl-2 (HDMEC-Bcl-2) as compared to co-culture with blank vector control (HDMEC-LXSN), oral squamous cell carcinoma- (OSCC3) and Kaposi’s sarcoma (SLK) showed increased invasiveness. HDMEC-Bcl-2 vascularized OSCC3 tumors showed higher local invasiveness compared to HDMEC-LXSN vascularized OSCC3 tumors as control. Both CXCL1 and CXCL8 play a positive regulatory role in primary endothelial cells and HDMEC-Bcl-2 exposed to vascular endothelial growth factor (VEGF). Of note, blocking CXCR2 signaling without hindering CXCR1 signaling suppressed invasion of OSCC3 and SLK to endothelial cells. These data demonstrate that CXC chemokines secreted by endothelial cells induce tumor cell invasion and that chemotactic signals generated by endothelial cells guide the outward diffusion of tumor cells observed in regional carcinogenesis.