The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
FEBS Open Bio. 2020 Dec;10(12):2687-2701. doi: 10.1002/2211-5463.13005. Epub 2020 Nov 9.
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.
肿瘤血管生成是肿瘤生长和转移所必需的。白细胞介素-35（IL-35）是 IL12 家族的一员，由 IL12A 和 EBV 诱导基因 3（EBI3）组成。据报道，升高的血浆 IL-35 水平与肿瘤的发生和发展有关。然而，IL-35 在胃癌（GC）血管生成中的作用尚不清楚。在这里，我们报告 IL-35 的表达与 GC 中的微血管密度升高、远处转移和不良预后相关。此外，进行了体外管形成试验以表明 IL-35 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 GC 细胞系中组织金属蛋白酶抑制剂 1 的表达，增强纤溶酶原激活物抑制剂 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 IL-35 参与血管生成，并与 GC 的不良预后相关。
