title: Dickkopf-1 expression is down-regulated during the colorectal adenoma-carcinoma sequence and correlates with reduced microvessel density and VEGF expression.
abstract: OBJECTIVE
  Dickkopf-1 (Dkk1), an antagonist of the Wnt-β-catenin signalling pathway, has been reported to play a role in cancer progression. However, little is known about the role of Dkk1 during the colorectal adenoma-carcinoma sequence. This study aimed to elucidate the role of Dkk1 in tumorigenesis and angiogenesis in colorectal cancer.
  
  
  RESULTS
  We examined Dkk1 expression immunohistochemically in 476 colorectal tissue samples, including 46 sets of matched specimens. Dkk1 expression was down-regulated during the colorectal adenoma-carcinoma sequence, both among the 476 samples and in the 46 sets of matched specimens. Dkk1 expression was correlated with decreased microvessel density (P < 0.05) and VEGF expression. In-vitro 3D coculture experiments showed that Dkk1 overexpression in HCT116 cells inhibited tube-like structure formation and down-regulated VEGF expression in human umbilical vein endothelial cells. Xenografts of Dkk1-overexpressing colorectal cancer cells were smaller, and showed lower microvessel density and VEGF expression levels, than those of control cells.
  
  
  CONCLUSIONS
  This study is the first to show the roles of Dkk1 during the colorectal adenoma-carcinoma sequence, which may involve suppression of the tumorigenesis and angiogenesis of CRC. Dkk1 could therefore serve as a potential target for tumour therapy.
authors.affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin Medical University, Tianjin, China.|National Clinical Research Centre for Cancer, Tianjin Medical University, Tianjin, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin Medical University, Tianjin, China.|National Clinical Research Centre for Cancer, Tianjin Medical University, Tianjin, China.|Department of Pathology, Tianjin Medical University, Tianjin, China.
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin Medical University, Tianjin, China.|National Clinical Research Centre for Cancer, Tianjin Medical University, Tianjin, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, China.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, China.
authors.forename: Danfang
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin Medical University, Tianjin, China.|National Clinical Research Centre for Cancer, Tianjin Medical University, Tianjin, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Dickkopf-1; adenoma-carcinoma sequence; angiogenesis; colorectal cancer; tumorigenesis