Expression of membrane cofactor protein (MCP, CD46) in human liver diseases

Abstract

Summary Membrane cofactor protein (MCP, CD46) is one of the complement regulatory proteins, and is widely distributed in human organs and protects cells from complement-mediated cytotoxicity. We analysed the distribution and the intensities of MCP in liver diseases and evaluated the role of MCP during hepatocarcinogenesis. Western blot analysis revealed that relative densities (density of the sample/density of the standard sample) of MCP in 27 HCC, 18 liver cirrhosis, nine chronic hepatitis and 12 normal liver were 0.63 ± 0.23, 0.21 ± 0.07, 0.25 ± 0.10 and 0.11 ± 0.03 (mean ± s.d.) respectively. MCP expression in hepatocellular carcinoma (HCC) was significantly higher than that in both liver cirrhosis and chronic hepatitis (P < 0.01). The difference in the tumour sizes, the grades of differentiation and viral marker status did not affect the expression. Immunohistological analysis revealed that MCP was distributed mainly in the basolateral membrane of the hepatic cord in non-cancerous liver, along with endothelial cells and bile duct cells. In HCC, the protein was observed on the membrane in a non-polarized fashion. These data suggest that HCC cells acquire the increased MCP expression in a development of HCC and may escape from tumour-specific complement-mediated cytotoxicity.

Engineered measles virus as a novel oncolytic viral therapy system for hepatocellular carcinoma

“…The results of these studies confirmed overexpression of CD46 in HCC tumor tissue compared to nonmalignant hepatic tissue. Our data are in concordance with an earlier study by Kinugasa et al, 43 which compared CD46 expression in normal human hepatic tissue, HCC, cirrhosis, and chronic hepatitis samples. Their results showed relative CD46 densities of 0.11 ϩ 0.1 in normal hepatic tissue, 0.63 ϩ 0.23 in HCC, 0.21 ϩ 0.07 in cirrhosis, and 0.25 ϩ 0.1 in chronic hepatitis.…”

“…57,58 The observation that CD46 expression is increased in cirrhosis, though still 3 times lower than in HCC, indicates clinical phase I toxicity studies are necessary. 43,52 In addition, our previous data showed that intraperitoneal treatment of Ifnar ™ -CD46Ge transgenic mice with MV-GFP did not result in significant transgene expression, despite the presence of MV-Edm RNA in liver tissue. 59 These data support the safety and suggest the tumor selectivity of MV-Edm.…”

The dual role of complement in cancer and its implication in anti-tumor therapy

“…Like most mCRPs, it is expressed on various tumors including head and neck squamous cell carcinoma (HNSCC) (102), hematological malignancies (93,103), breast, prostate (104), ovarian (105,106), glioma (107), liver (108), renal (25) and cervical cancer (109) among others. Together with CD55, downregulation of CD46 with siRNA resulted in increased CDC in a number of cell lines (99,110).…”

Evaluation of adenovirus vectors containing serotype 35 fibers for tumor targeting

“…Recently, relative resistance of malignant tumor cells to infection with Ad5-based vectors has been connected to downregulation of CAR and/or integrin expression on target cell membranes. [4][5][6][7] Group B Ad serotypes (Ad3, 7,11,14,16,21,34,35,50) use a receptor other than CAR. We and others recently identified CD46 as a cellular receptor that is used by most B-group Ads.…”