title: [Effect of colon cancer cell-derived IL-1α on the migration and proliferation of vascular endothelial cells].
abstract: OBJECTIVE
  To explore the effect of colon cancer cell-derived interleukin-1α on the migration and proliferation of human umbilical vein endothelial cells as well as the role of IL-1α and IL-1ra in the angiogenesis process.
  
  
  METHODS
  Western blot was used to detect the expression of IL-1α and IL-1R1 protein in the colon cancer cell lines with different liver metastatic potential. We also examined how IL-1α and IL-1ra influence the proliferation and migration of umbilical vascular endothelial cells assessed by PreMix WST-1 assay and migration assay, respectively. Double layer culture technique was used to detect the effect of IL-1α on the proliferation and migration of vascular endothelial cells and the effect of IL-1ra on the vascular endothelial cells.
  
  
  RESULTS
  Western blot analysis showed that IL-1α protein was only detected in highly metastatic colon cancer HT-29 and WiDr cells, but not in the lowly metastatic CaCo-2 and CoLo320 cells.Migration assay showed that there were significant differences in the number of penetrated cells between the control (17.9±3.6) and 1 ng/ml rIL-1α group (23.2±4.2), 10 ng/ml rIL-1α group (31.7±4.5), and 100 ng/ml rIL-1α group (38.6±4.9), showing that it was positively correlated with the increasing concentration of rIL-1α (P<0.01 for all). The proliferation assay showed that the absorbance values were 1.37±0.18 in the control group, and 1.79±0.14 in the 1 ng/ml rIL-1α group, 2.14±0.17 in the 10 ng/ml rIL-1α group, and 2.21±0.23 in the 100 ng/ml rIL-1α group, showing a positive correlation with the increasing concentration of rIL-1α(P<0.01 for all). IL-1ra significantly inhibited the proliferation and migration of vascular endothelial cells (P<0.01). The levels of VEGF protein were (1.697±0.072) ng/ml, (3.507±0.064)ng/ml and (4.139±0.039)ng/ml in the control, HUVECs+ IL-1α and HUVECs+ HT-29 co-culture system groups, respectively, showing a significant difference between the control and HUVECs+ 10 pg/ml rIL-1α groups and between the control and HUVECs+ HT-29 groups (P<0.01 for both).
  
  
  CONCLUSIONS
  Our findings indicate that colon cancer cell-derived IL-1α plays an important role in the liver metastasis of colon cancer through increased VEGF level of the colon cancer cells and enhanced vascular endothelial cells proliferation, migration and angiogenesis, while IL-1ra can suppress the effect of IL-1α and inhibit the angiogenesis in colon cancer.
authors.affiliation: Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China.
authors.forename: Jiachi
authors.initials: J
authors.lastname: Ma
authors.affiliation: Email: 13919093907@126.com.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Gu
authors.forename: Yiping
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.forename: Meiling
authors.initials: M
authors.lastname: Liu
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Chen
authors.forename: Qingjin
authors.initials: Q
authors.lastname: Guo
authors.forename: Shixun
authors.initials: S
authors.lastname: Ma
mesh_terms: D015153:Blotting, Western; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism / Q000502:physiology*; D053582:Interleukin-1alpha / Q000378:metabolism / Q000502:physiology*; D008113:Liver Neoplasms / Q000556:secondary; D009389:Neovascularization, Pathologic / Q000209:etiology*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha