title: IL-17 and insulin/IGF1 enhance adhesion of prostate cancer cells to vascular endothelial cells through CD44-VCAM-1 interaction.
abstract: BACKGROUND
  Extravasation is a critical step in cancer metastasis, in which adhesion of intravascular cancer cells to the vascular endothelial cells is controlled by cell surface adhesion molecules. The role of interleukin-17 (IL-17), insulin, and insulin-like growth factor 1 (IGF1) in adhesion of prostate cancer cells to the vascular endothelial cells is unknown, which is the subject of the present study.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) and human prostate cancer cell lines (PC-3, DU-145, LNCaP, and C4-2B) were analyzed for expression of vascular cell adhesion molecule 1 (VCAM-1), integrins, and cluster of differentiation 44 (CD44) using flow cytometry and Western blot analysis. The effects of IL-17, insulin, and IGF1 on VCAM-1 expression and adhesion of prostate cancer cells to HUVECs were examined. The interaction of VCAM-1 and CD44 was assessed using immunoprecipitation assays.
  
  
  RESULTS
  Insulin and IGF1 acted with IL-17 to increase VCAM-1 expression in HUVECs. PC-3, DU-145, LNCaP, and C4-2B cells expressed β1 integrin but not α4 integrin. CD44 was expressed by PC-3 and DU-145 cells but not by LNCaP or C4-2B cells. When HUVECs were treated with IL-17, insulin or IGF1, particularly with a combination of IL-17 and insulin (or IGF1), adhesion of PC-3 and DU-145 cells to HUVECs was significantly increased. In contrast, adhesion of LNCaP and C4-2B cells to HUVECs was not affected by treatment of HUVECs with IL-17 and/or insulin/IGF1. CD44 expressed in PC-3 cells physically bound to VCAM-1 expressed in HUVECs.
  
  
  CONCLUSIONS
  CD44-VCAM-1 interaction mediates the adhesion between prostate cancer cells and HUVECs. IL-17 and insulin/IGF1 enhance adhesion of prostate cancer cells to vascular endothelial cells through increasing VCAM-1 expression in the vascular endothelial cells. These findings suggest that IL-17 may act with insulin/IGF1 to promote prostate cancer metastasis.
authors: Department of Structural and Cellular Biology, Tulane University, New Orleans, Louisiana.
authors: Chong
authors: C
authors: Chen
authors: Qiuyang
authors: Q
authors: Zhang
authors: Sen
authors: S
authors: Liu
authors: Keshab R
authors: KR
authors: Parajuli
authors: Yine
authors: Y
authors: Qu
authors: Jiandong
authors: J
authors: Mei
authors: Zhiquan
authors: Z
authors: Chen
authors: Hui
authors: H
authors: Zhang
authors: Damir B
authors: DB
authors: Khismatullin
authors: Zongbing
authors: Z
authors: You
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020381:Interleukin-17 / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C583557:IGF1 protein, human; D007328:Insulin; D020381:Interleukin-17; D019010:Vascular Cell Adhesion Molecule-1; D007334:Insulin-Like Growth Factor I
keywords: IGF1; IL-17; VCAM-1; insulin; prostate cancer metastasis