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Review
. 2013:2013:968041.
doi: 10.1155/2013/968041. Epub 2013 Apr 22.

CUZD1 and anti-CUZD1 antibodies as markers of cancer and inflammatory bowel diseases

Christos Liaskos  1 , Eirini I Rigopoulou, Timoklia Orfanidou, Dimitrios P Bogdanos, Christos N Papandreou
Affiliations
Review

CUZD1 and anti-CUZD1 antibodies as markers of cancer and inflammatory bowel diseases

Christos Liaskos et al. Clin Dev Immunol. 2013.

Abstract

CUZD1, the CUB, and zona pellucida-like domains-containing protein 1, is a newly identified antigen of pancreatic autoantibodies (PAB) giving a reticulogranular pattern in patients with inflammatory bowel diseases, and in particular Crohn's disease. The exact mechanisms by which this pancreatic antigen becomes the target of IBD-specific pancreatic autoantibodies are unclear. At the same time, evolving data strongly support a role for CUZD1 in carcinogenesis. Human CUZD1 is mapped at chromosome 10q26.13 and the loss of this region is a frequent event in various malignant tumours. mRNA overexpression of CUZD1 has been noted in ovarian cancer and serum levels of CUZD1 are elevated in women with ovarian cancer and patients suffering from pancreatic cancer. CUZD1 appears to be one of the relatively few biomarkers that serve as both cancer biomarker and autoantigen of autoantibodies in an autoimmune disease unrelated to cancerous organs. This review discusses the role of CUZD1 in cancer and autoimmunity. We anticipate that a better understanding of the function of CUZD1 will help us to understand how it becomes the focus of an autoimmune attack specifically targeting the intestine and its enigmatic role in carcinogenesis.

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Figures

Figure 1
Figure 1
Amino acid comparison between human CUZD1 and DMBT1. There is a high degree of homology between the two proteins possibly reflecting the similarity between the CUB and ZP domains contained in both. The comparison has been performed using the BLASTp2 protein-protein programme. Top row: CUZD1; bottom row: DMTB1.
Figure 2
Figure 2
CUZD1 protein features including the CUB and ZP domain exact positioning within the protein.
Figure 3
Figure 3
Multiple amino acid sequence alignment of CUZD1 of various species shows striking conservation. Sequences aligned include Rattus norvegicus (EDM 11686.1), Homo sapiens (NP_071317.2), Pan troglodytes (XP_001160209.2), Macaca fascicularis (EHH 65083.1), and Canis lupus familiaris (XP_544054.2). Asterisk indicates identities and semicolon indicates conserved or semiconserved substitutions. The alignment has been performed using the CLUSTAL W (1.83) multiple sequence alignment tool.
Figure 4
Figure 4
Immunofluorescence staining patterns of CUZD1-specific pancreatic autoantibodies giving a reticulogranular pattern using pancreatic tissue (a) or CUZD1-overexressed HEK3 cells (b).
See this image and copyright information in PMC

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