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. 2009 Aug 4;101(3):492-7.
doi: 10.1038/sj.bjc.6605163. Epub 2009 Jul 14.

High expression of HSP47 in ulcerative colitis-associated carcinomas: proteomic approach

K Araki  1 , T Mikami, T Yoshida, M Kikuchi, Y Sato, M Oh-ishi, Y Kodera, T Maeda, I Okayasu
Affiliations

High expression of HSP47 in ulcerative colitis-associated carcinomas: proteomic approach

K Araki et al. Br J Cancer. .

Abstract

Background: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease, known to be associated with a markedly increased risk of colorectal carcinoma development.

Methods: Using proteomic analysis with two-dimensional gel electrophoresis and mass spectrometry, differentially expressed proteins were assessed between UC-associated cancer and sporadic colon cancer cell lines. Western blot and immunostaining were performed for confirming the expression.

Results: Heat-shock protein of 47 kDa (HSP47) was identified as one of the proteins expressed more highly in UC-associated cancer cell lines, and an immunohistochemical examination confirmed significantly higher levels of HSP47 in UC-associated colon cancers than in sporadic counterparts, the expression increasing with a progression of neoplastic lesions. Heat-shock protein of 47 kDa was further found to be coexpressed with type I collagen in the cytoplasm, and both HSP47 and type I collagen were released from cultured cells into the culture medium.

Conclusion: These results suggest that overexpression of HSP47 is a unique characteristic of UC-associated carcinoma related to type I collagen synthesis, with possible clinical applications.

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Figures

Figure 1
Figure 1
Agarose two-dimensional electrophoresis gel patterns of cell lines. (A) Representative proteome maps derived from the UCCA-3, UC-associated cancer cell line. The red circle indicates the protein spot, HSP47. (B) The zoomed two-dimensional electrophoresis gel images show expression of HSP47. UC-associated cancer cell lines show an increased expression of HSP47 compared with sporadic cancer cell lines (Coomassie blue-stained two-dimensional electrophoresis gels).
Figure 2
Figure 2
Western blot analysis of the HSP47 expression in cell lines. (A) UC-associated cancer cell lines (UC-Ca) and sporadic cancer cell lines (Sp-Ca). β-Actin expression was used as a control. (B) Immunocytochemical staining of HSP47 in the six cell lines. The strong reactions in UC-associated cancer cell lines is noted.
Figure 3
Figure 3
Immunohistochemical staining of HSP47 in tissues. (A) UC-associated lesions and normal mucosa. Normal epithelial cells are not stained for HSP47. It is noted that the increased expression of HSP47 with progression through to carcinoma is apparent. (B) A higher magnification of the boxed area is shown in panel A. UCLGD, UC low-grade dysplasia; UCHGD, UC, high-grade dysplasia; UCCA, UC-associated adenocarcinoma.
Figure 4
Figure 4
The epithelial expression of HSP47 in UC-associated (open bars) and sporadic colon tumour lesions (hatched bars). Data are mean scores and s.d. (a) P<0.05; (b) P<0.01; and (c) P<0.001; LGD, low-grade dysplasia; HGD, high-grade dysplasia.
Figure 5
Figure 5
Double immunofluorescence staining for HSP47 (red-rhodamin) and type I collagen (green-FITC) in a UC-associated cancer cell line (UCCA-3) and a sporadic cancer cell line (KE-24). The cells were counterstained with DAPI to visualise the nuclei.
Figure 6
Figure 6
Collagen synthesis of UC-associated cancer cell lines (UC-Ca) (open bars), sporadic cancer cell lines (Sp-Ca ) (hatched bars), and human fibroblast cells (black bars). Data are given as concentrations of type I collagen in medium. Vertical lines show s.d.
Figure 7
Figure 7
Western blot of HSP47 in cell culture medium. An increased release of HSP47 was shown in UC-associated cancer cell lines than in sporadic colorectal cancer cell lines.
See this image and copyright information in PMC

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