Transformation of Human Umbilical Vein Endothelial Cells Induced by the Tumor Microenvironment of Nephroblastoma Cells

作者全名："Sang, Bo-tao; Wang, Chang-dong; Guo, Jia-qi; Wu, Xiang-mei"

作者地址："[Sang, Bo-tao; Wang, Chang-dong; Guo, Jia-qi; Wu, Xiang-mei] Chongqing Med Univ, Basic Med Coll, Mol Med & Canc Res Ctr, Chongqing, Peoples R China; [Sang, Bo-tao; Guo, Jia-qi; Wu, Xiang-mei] Chongqing Med Univ, Basic Med Coll, Dept Physiol, Chongqing, Peoples R China; [Wang, Chang-dong] Chongqing Med Univ, Basic Med Coll, Dept Biochem & Mol Biol, Chongqing, Peoples R China"

通信作者："Wu, XM (通讯作者)，Chongqing Med Univ, Basic Med Coll, Mol Med & Canc Res Ctr, Chongqing, Peoples R China.; Wu, XM (通讯作者)，Chongqing Med Univ, Basic Med Coll, Dept Physiol, Chongqing, Peoples R China."

来源：JOURNAL OF EVOLUTIONARY BIOCHEMISTRY AND PHYSIOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000979487900009

JCR分区：Q4

影响因子：0.6

年份：2023

卷号：59

期号：2

开始页：411

结束页：419

文献类型：Article

关键词：nephroblastoma; human umbilical vein endothelial cells (HUVEC); tumor endothelial cells; angiogenesis; PI3K; AKT signaling pathway

摘要："Nephroblastoma is one of the most common renal malignanciesin children, and tumor angiogenesis increases the risk of metastasisand recurrence. This study investigated the effect of the tumormicroenvironment on angiogenesis in nephroblastoma cell and itsmolecular mechanism. The indirect co-culture model of human umbilicalvein endothelial cells (HUVECs) was established using a conditionedmedium from the nephroblastoma cell line G401. Cell medium was collectedto prepare tumor-conditioned medium (TCM), which was applied toHUVECs. Western blotting and immunofluorescence assays were usedto analyze the expression of tumor endothelial marker 8 (TEM8) andthe elements phosphatidylinositol 3-kinase (PI3K)/protein kinaseB (PKB)/AKT signaling pathway at the protein level. In addition,the proliferation, invasion, migration, and tube formation of HUVECsafter induction by TCM were analyzed by the Cell Counting Kit-8 (CCK-8),as well as by transwell invasion, wound-healing, and matrigel tubeformation assays. Compared with that of the control group, the expressionof TEM8, p-PI3K/PI3K, and p-AKT/AKT was increased, and proliferation,invasion, migration, and tubulogenesis were significantly enhancedin HUVECs induced by TCM. A PI3K pathway inhibitor (LY294002) weakenedthe canalization of HUVECs. These findings suggest that the nephroblastomamicroenvironment can promote the transformation of endothelial cells(ECs) into tumor endothelial cells (TECs), significantly enhancingtheir proliferation, invasion, migration, and tubular formation,and this effect may be related to the PI3K/AKT signaling pathway."

基金机构："Program for Youth Innovation in Future Medicine, Chongqing Medical University; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN201900408]"

基金资助正文："This research was supported by Program for Youth Innovation in Future Medicine, Chongqing Medical University, Scientific and Technological Research Program of Chongqing Municipal Education Commission (grant no.KJQN201900408, 2019)."