Tumor angiogenesis is required for tumor growth and metastasis. Interleukin‐35 (IL35), a member of the IL12 family, is a dimer composed of IL12A and EBV‐induced gene 3（EBI3）. Elevated plasma IL35 levels have been reported to be associated with the occurrence and development of tumors. However, the role of IL35 in the angiogenesis of gastric cancer (GC) is still unclear. Here, we report that expression of IL35 is correlated with higher microvessel density, distant metastasis and poor prognosis in GC. Moreover, in vitro tube formation assays were performed to show that IL35 may contribute to the tube formation abilities of human umbilical vein endothelial cells. IL12A was observed to be the dominant subunit in promotion of tube formation. IL12A also inhibited expression of tissue inhibitor of metalloproteinase 1 and enhanced expression of plasminogen activator inhibitor 1 and insulin‐like growth factor‐binding protein 1 in a GC cell line. In conclusion, our data suggest that IL35 is involved in angiogenesis and is associated with poor prognosis for GC.

中文翻译：

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IL35 通过改变 TIMP1、PAI1 和 IGFBP1 预测胃癌的预后并与血管生成相关

肿瘤血管生成是肿瘤生长和转移所必需的。白细胞介素-35 (IL35) 是 IL12 家族的一员，是由 IL12A 和 EBV 诱导基因 3（EBI3）组成的二聚体。据报道，血浆 IL35 水平升高与肿瘤的发生和发展有关。然而，IL35在胃癌（GC）血管生成中的作用仍不清楚。在这里，我们报告 IL35 的表达与 GC 中较高的微血管密度、远处转移和不良预后相关。此外，体外进行管形成试验以表明 IL35 可能有助于人脐静脉内皮细胞的管形成能力。观察到 IL12A 是促进管形成的主要亚基。IL12A 还抑制金属蛋白酶 1 组织抑制剂的表达，并增强 GC 细胞系中纤溶酶原激活剂抑制剂 1 和胰岛素样生长因子结合蛋白 1 的表达。总之，我们的数据表明 IL35 参与血管生成并与 GC 的不良预后相关。