Elucidation of the roles of tumor necrosis factor and chemokines in inflammation-associated carcinogenesis

我们研究了趋化因子在小鼠肿瘤模型中的病理生理作用。我们证实了在偶氮甲烷和葡聚糖硫酸钠联合致癌过程中，结肠组织中产生了一种趋化因子CCL2。产生的CCL2诱导表达环氧合酶-2的巨噬细胞迁移，从而促进肿瘤的发生和发展。此外，在同一致癌步骤中产生了另一种趋化因子CCL3，并在该过程的后期阶段促成了纤维化的建立。相反，我们观察到，静脉注射CCL3可以增强射频消融小鼠肝癌后的抗肿瘤效果，这可以触发树突状细胞向消融部位的迁移，从而诱导肿瘤特异性免疫。因此，与内源性产生的CCL3相比，药理剂量的CCL3可能通过调节树突状细胞的迁移过程来诱导肿瘤特异性免疫。

We investigated the pathophysiological roles of chemokines in mouse tumor models. We proved that a chemokine, CCL2, was produced in colon tissues during the course of carcinogenesis process caused by the combined treatment of azoxymethane and dextran sodium sulfate. The produced CCL2 induced the migration of cyclooxygenase-2-expressing macrophages, thereby contributing to the development and progression of carcinomas. Moreover, another chemokine, CCL3, was produced in the same carcinogenesis step and contributed to the establishment of fibrosis in the later phase of the process. On the contrary, we observed that anti-tumor effects after radiofrequency ablation of mouse hepatoma were augmented by an intravenous injection of CCL3, which could trigger the migration of dendritic cells into the ablated sites, thereby inducing a tumor-specific immunity. Thus, in contrast to endogenously produced CCL3, a pharmacological dose of CCL3 may induce tumor-specific immunity by regulating the migratory process of dendritic cells.