Analysis of the effect of human lymphatic endothelial cells on proteins secreted by epithelial ovarian cancer cells with lymph node-oriented metastasis / 中国肿瘤临床

ABSTRACT

Objective:This study aimed to investigate the effect of human lymphatic endothelial cells (HLECs) on proteins secreted by epithelial ovarian cancer (EOC) cells SKOV3-pm4 with highly directional lymphatic metastasis. Methods:The supernatants of the four groups of cultured cells (A, SKOV3;B, SKOV3+HLEC;C, SKOV3-PM4;and D, SKOV3-PM4+HLEC) were collected. The proteins of these cells were detected by antibody arrays and iTRAQ-2D-LC-MALDI-TOF/TOF/MS. The screened significantly differential proteins were further analyzed by bioinformatics and validated in the human serum and cell culture medium by ELISA. Results:Progranulin (GRN) and vascular endothelial growth factor A (VEGF-A) were upregulated between groups C and A. In addition, insulin-like growth factor binding protein-7 (IGFBP-7) and secreted protein acid rich in cysteine (SPARC) were downregulated between groups D and C. Comprehensive bioinformatics analysis revealed that IGFBP7 interacted with VEGFA. VEGF exhibited the highest expression in ovarian cancer and IGFBP7 exhibited the lowest expression compared with the serum of the normal control group. Statistically significant differences were observed between the two substances. Conclusion:The HLEC microenvironment is closely associated with directional metastasis in lymph nodes with differential proteins, including matricellular proteins and adhesion factors. In particular, the upregulation of VEGFA and GRN and the downregulation of SPARC and IGFBP7 were closely associated with the directional metastasis of EOC cells in lymph nodes.