Dickkopf-3 as a new potential marker for neoangiogenesis in colorectal cancer: expression in cancer tissue and adjacent non-cancerous tissue.
Gene expression of Dickkopf-3 (Dkk-3) has been shown to be upregulated in tumor endothelium of colorectal cancer (CRC). For the first time, we analyzed Dkk-3 protein expression in CRC and its potential as a marker for neoangiogenesis. We used tissue microarrays (TMAs) to investigate Dkk-3 in microvessels of 403 CRC samples, 318 appropriate adjacent non-cancerous samples and 127 normal colorectal samples. Of cancer samples with CD31-positive microvessels, 67.7% were positive for Dkk-3. Dkk-3 staining was demonstrated in endothelial cells of all microvessels in nearly all cases. Dkk-3-positive samples showed a higher mean microvessel count than did Dkk-3-negative samples (P=0.001). Dkk-3 expression increased with rising numbers of microvessels per sample (P<0.0001). In adjacent samples with CD31-positive microvessels, 56% were Dkk-3-positive in all microvessels. Similar to cancer samples, Dkk-3-positive adjacent samples had a higher mean microvessel count than did Dkk-3-negative samples (P<0.0001), and Dkk-3 expression also increased with rising numbers of microvessels (P<0.0001). All microvessels in normal mucosa samples were negative for Dkk-3. Dkk-3 can be considered a putative pro-angiogenic protein in neovascularization and may possibly be a marker for neoangiogenesis in CRC. Further investigations will elucidate whether Dkk-3 is a target structure for novel therapies.
Zitt
Matthias
M
Department of General and Transplant Surgery, Innsbruck Medical University, Innsbruck, Austria. matthias.zitt@i-med.ac.at
Untergasser
Gerold
G
Amberger
Albert
A
Moser
Patrizia
P
Stadlmann
Sylvia
S
Zitt
Marion
M
Müller
Hannes M
HM
Mühlmann
Gilbert
G
Perathoner
Alexander
A
Margreiter
Raimund
R
Gunsilius
Eberhard
E
Ofner
Dietmar
D
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018925:Chemokines; D003106:Colon / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000098:blood supply*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D007413:Intestinal Mucosa / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D012007:Rectum / Q000737:chemistry
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins