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Focal overexpression of insulin-like growth factor 2 by hepatocytes and cholangiocytes in viral liver cirrhosis.

Sedlaczek N, Hasilik A, Neuhaus P, Schuppan D, Herbst H - Br. J. Cancer (2003)

Bottom Line: High focal levels of IGF-2 RNA were found in some hepatocytes of all livers with HBV- or HCV-induced cirrhosis (n=10), but in only one of the cirrhoses with nonviral aetiology (n=8).Compared with noncirrhotic liver, all cirrhotic specimens showed reduced hepatocellular expression of M6P/IGF-2R protein, which contrasted with enhanced expression in perisinusoidal cells.Immunostaining for the other antigens did not reveal significant differences.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University of Muenster, Germany.

ABSTRACT
Insulin-like growth factor (IGF)-2 is overexpressed in hepatocellular carcinoma and accompanying dysplastic lesions. IGF-2 signalling is mediated through IGF-1 receptor (IGF-1R), while mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF-2R) controls pericellular levels of free IGF-2. We studied, by in situ hybridisation and immunohistology, 18 liver specimens with cirrhosis of different aetiology without neoplastic or dysplastic lesions. Immunohistology was also performed for insulin receptor IGF-1R and IGF-binding proteins 3 and 4. High focal levels of IGF-2 RNA were found in some hepatocytes of all livers with HBV- or HCV-induced cirrhosis (n=10), but in only one of the cirrhoses with nonviral aetiology (n=8). IGF-2 was overexpressed in biliary duct epithelial cells in one case. Compared with noncirrhotic liver, all cirrhotic specimens showed reduced hepatocellular expression of M6P/IGF-2R protein, which contrasted with enhanced expression in perisinusoidal cells. Immunostaining for the other antigens did not reveal significant differences. Upregulation of IGF-2 in some hepatocytes may lead to high focal IGF-2 levels sufficient to saturate local IGF-2 binding capacities, and may result in an increased susceptibility to cellular dedifferentiation and, ultimately, liver cancer. Downregulation of hepatocellular M6P/IGF-2R and upregulation of IGF-2 seem to be early events in hepatocarcinogenesis prior to the appearance of morphologically distinct dysplastic lesions. Elevated focal IGF-2 transcript levels may therefore indicate an increased risk for hepatocellular and cholangiocellular carcinomas.

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Related in: MedlinePlus

Immunostaining for the M6P/IGF-2R on normal (A) and cirrhotic liver (B, HCV-related cirrhosis) with the IGF-receptor-2 antibody 2C2. Normal liver displays cytoplasmic and membrane-specific immunostaining of hepatocytes (A). Cirrhosis related to HCV infection shows reduced immunostaining of hepatocytes restricted to the sinusoidal part of the cell membrane as well as increased signals in perisinusoidal cells (B).
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fig2: Immunostaining for the M6P/IGF-2R on normal (A) and cirrhotic liver (B, HCV-related cirrhosis) with the IGF-receptor-2 antibody 2C2. Normal liver displays cytoplasmic and membrane-specific immunostaining of hepatocytes (A). Cirrhosis related to HCV infection shows reduced immunostaining of hepatocytes restricted to the sinusoidal part of the cell membrane as well as increased signals in perisinusoidal cells (B).

Mentions: In normal liver, the antibody 2C2 produced a diffuse cytoplasmic and membraneous staining of hepatocytes (Figure 2AFigure 2


Focal overexpression of insulin-like growth factor 2 by hepatocytes and cholangiocytes in viral liver cirrhosis.

Sedlaczek N, Hasilik A, Neuhaus P, Schuppan D, Herbst H - Br. J. Cancer (2003)

Immunostaining for the M6P/IGF-2R on normal (A) and cirrhotic liver (B, HCV-related cirrhosis) with the IGF-receptor-2 antibody 2C2. Normal liver displays cytoplasmic and membrane-specific immunostaining of hepatocytes (A). Cirrhosis related to HCV infection shows reduced immunostaining of hepatocytes restricted to the sinusoidal part of the cell membrane as well as increased signals in perisinusoidal cells (B).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376349&req=5

fig2: Immunostaining for the M6P/IGF-2R on normal (A) and cirrhotic liver (B, HCV-related cirrhosis) with the IGF-receptor-2 antibody 2C2. Normal liver displays cytoplasmic and membrane-specific immunostaining of hepatocytes (A). Cirrhosis related to HCV infection shows reduced immunostaining of hepatocytes restricted to the sinusoidal part of the cell membrane as well as increased signals in perisinusoidal cells (B).
Mentions: In normal liver, the antibody 2C2 produced a diffuse cytoplasmic and membraneous staining of hepatocytes (Figure 2AFigure 2

Bottom Line: High focal levels of IGF-2 RNA were found in some hepatocytes of all livers with HBV- or HCV-induced cirrhosis (n=10), but in only one of the cirrhoses with nonviral aetiology (n=8).Compared with noncirrhotic liver, all cirrhotic specimens showed reduced hepatocellular expression of M6P/IGF-2R protein, which contrasted with enhanced expression in perisinusoidal cells.Immunostaining for the other antigens did not reveal significant differences.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University of Muenster, Germany.

ABSTRACT
Insulin-like growth factor (IGF)-2 is overexpressed in hepatocellular carcinoma and accompanying dysplastic lesions. IGF-2 signalling is mediated through IGF-1 receptor (IGF-1R), while mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF-2R) controls pericellular levels of free IGF-2. We studied, by in situ hybridisation and immunohistology, 18 liver specimens with cirrhosis of different aetiology without neoplastic or dysplastic lesions. Immunohistology was also performed for insulin receptor IGF-1R and IGF-binding proteins 3 and 4. High focal levels of IGF-2 RNA were found in some hepatocytes of all livers with HBV- or HCV-induced cirrhosis (n=10), but in only one of the cirrhoses with nonviral aetiology (n=8). IGF-2 was overexpressed in biliary duct epithelial cells in one case. Compared with noncirrhotic liver, all cirrhotic specimens showed reduced hepatocellular expression of M6P/IGF-2R protein, which contrasted with enhanced expression in perisinusoidal cells. Immunostaining for the other antigens did not reveal significant differences. Upregulation of IGF-2 in some hepatocytes may lead to high focal IGF-2 levels sufficient to saturate local IGF-2 binding capacities, and may result in an increased susceptibility to cellular dedifferentiation and, ultimately, liver cancer. Downregulation of hepatocellular M6P/IGF-2R and upregulation of IGF-2 seem to be early events in hepatocarcinogenesis prior to the appearance of morphologically distinct dysplastic lesions. Elevated focal IGF-2 transcript levels may therefore indicate an increased risk for hepatocellular and cholangiocellular carcinomas.

Show MeSH
Related in: MedlinePlus