Cancer cells can communicate with the tumor microenvironment and contribute to tumor progression. However, the effects of drug-resistant tumor cells on angiogenesis are unclear. Current anti-angiogenic strategies also have limitations and it would be useful to develop novel targets and treatment strategies. Here, our study showed that the conditioned medium and exosomes from 5-FU-resistant colon cancer cells promoted angiogenesis, and we observed that exosomal dipeptidyl peptidase IV (DPP4) was a potent inducer of this angiogenesis. DPP4-enriched exosomes increased periostin (POSTN) expression in human umbilical vein endothelial cells via Twist1 nuclear translocation or activating Smad signaling pathway, while silencing or inhibition of DPP4 neutralized those effects. The in vivo and clinical data indicated that high DPP4 expression was related to tumor progression. These findings indicate that DPP4 may be a target for inhibiting angiogenesis in 5-FU-resistant colon cancer. Furthermore, exosomal DPP4 concentrations may be a useful prognostic marker for colon cancer.

癌细胞可以与肿瘤微环境通讯并促进肿瘤进展。然而，耐药肿瘤细胞对血管生成的作用尚不清楚。当前的抗血管生成策略也有局限性，开发新的靶标和治疗策略将很有用。在这里，我们的研究表明，来自5-FU耐药结肠癌细胞的条件培养基和外泌体促进了血管生成，并且我们观察到外泌体二肽基肽酶IV（DPP4）是这种血管生成的有效诱导剂。富含DPP4的外泌体通过Twist1核易位或激活Smad信号通路增加了人脐静脉内皮细胞的骨膜素（POSTN）表达，而沉默或抑制DPP4则抵消了这些作用。体内和临床数据表明，高DPP4表达与肿瘤进展有关。这些发现表明DPP4可能是抑制5-FU耐药结肠癌中血管生成的靶标。此外，外体DPP4浓度可能是结肠癌的有用的预后指标。