Abstract:
Objective:To investigate the effect of DKK 1 on linearly patterned programmed cell necrosis (LPPCN) and vasculogenic mim-icry (VM) and the related molecular mechanism in non- small cell lung cancer (NSCLC). Methods:A total of 173 human NSCLC speci-mens were collected to detect LPPCN by H & E staining, detect VM with CD31/PAS double staining, and investigate DKK1 and related protein expression by immunohistochemistry. The clinical pathological significance of LPPCN, VM, and DKK 1 and the correlation of them were analyzed. Human NSCLC H 460 -DKK1 cells were engrafed in nude mice to evaluate the influence of DKK1 up-regulation on VM and LPPCN in vivo. Results:Approximately,14. 45% (25/173 ) of NSCLC had VM and 49. 71% (86/173 ) had LPPCN. 25. 6% (22/86) of NSCLC cases in LPPCN - positive group formed VM. Both of VM and LPPCN were all correlated with poor differentiation, late TNM stage, easy recurrence and metastasis and poor prognosis in NSCLC. DKK 1 expression in the VM-positive group and the LPPCN-positive group was higher than that in the VM-negative group and the LPPCN-negative group, respectively. DKK 1, LPPCN, and VM were positive -ly correlated with VE-cadherin, MMP- 2, β -catenin nuclear expression and Twist 1. H460 -DKK1 transplantation tumor model confirmed that DKK 1 promotes the expression of VM and LPPCN and related proteins in NSCLC. Conclusion: The increase of theβ - catenin and Twist1 expression induced by DKK 1 may promote the formation of LPPCN and VM in NSCLC.