The Expressions of Nerve Growth Factor and Its Receptor p75NGFR in Hepatocellular Carcinoma: Their Relation with the Clinicopathologic Factors
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Background : Nerve growth factor (NGF) has been suggested to participate in tumor progression and it can interact with its receptor p75NGFR. In the present study, we investigated the expressions of NGF and p75NGFR in hepatocellular carcinoma (HCC). Methods : We performed immunohistochemistry for NGF, p75NGFR and PCNA in 45 cases of HCCs, and examined the relationships between the clinicopathologic factors and the immunohistochemical results. Results : NGF was detected in 84.4% (38/45) of the tumor cells and in 64.4% (29/45) of the non-tumorous hepatocytes. Furthermore, a NGF expression was present in 28.9% (13/45) of the endothelial cells in the HCCs, but in 80% (36/45) of the endothelial cells in the non-tumor liver tissue. The tumor cells were negative for p75NGFR in all the HCCs. Although a p75NGFR expression was present in all the nerve fibers in the non-tumor liver tissues, it was markedly reduced (42.2%; 19/45) in the HCCs and a p75NGFR expression was observed at the sinusoids or around the large vessels. The HCCs expressing NGF, either in the tumor cells or the endothelial cells, showed a larger size than those HCCs that didn’t express NGF. The NGF positive tumors showed a tendency toward a higher PCNA-labeling index than did the negative tumors. Conclusions : The changed localization of the NGF expression and the decreased expression of p75NGFR are associated with hepatic carcinogenesis. We suggest that a NGF expression may contribute to the progression of HCC.
Abstract
Background : Nerve growth factor (NGF) has been suggested to participate in tumor progression and it can interact with its receptor p75NGFR. In the present study, we investigated the expressions of NGF and p75NGFR in hepatocellular carcinoma (HCC). Methods : We performed immunohistochemistry for NGF, p75NGFR and PCNA in 45 cases of HCCs, and examined the relationships between the clinicopathologic factors and the immunohistochemical results. Results : NGF was detected in 84.4% (38/45) of the tumor cells and in 64.4% (29/45) of the non-tumorous hepatocytes. Furthermore, a NGF expression was present in 28.9% (13/45) of the endothelial cells in the HCCs, but in 80% (36/45) of the endothelial cells in the non-tumor liver tissue. The tumor cells were negative for p75NGFR in all the HCCs. Although a p75NGFR expression was present in all the nerve fibers in the non-tumor liver tissues, it was markedly reduced (42.2%; 19/45) in the HCCs and a p75NGFR expression was observed at the sinusoids or around the large vessels. The HCCs expressing NGF, either in the tumor cells or the endothelial cells, showed a larger size than those HCCs that didn’t express NGF. The NGF positive tumors showed a tendency toward a higher PCNA-labeling index than did the negative tumors. Conclusions : The changed localization of the NGF expression and the decreased expression of p75NGFR are associated with hepatic carcinogenesis. We suggest that a NGF expression may contribute to the progression of HCC.
참고문헌 (29)
- Tiniakos DG, "Innervation of the liver: morphology and function", Liver, 16, pp.151~160 (1996)
- Kyosola K, "Adrenergic innervation of the human liver: a fluorescence histochemical analysis of clinical liver biopsy specimens", Scand J Gastroenterol, 20, pp.254~256 (1985)
- Hartmann H, "Direct control of glycogen metabolism in the perfused rat liver by the sympathetic innervation", Eur J Biochem, 123, pp.521~526 (1982)
- Fahnestock M, "Structure and biosynthesis of nerve growth factor", Curr Top Microbiol Immunol, 165, pp.1~26 (1991)
- Maness LM, "The neurotrophins and their receptors: structure, function, and neuropathology", Neurosci Biobehav Rev, 18, pp.143~159 (1994)
- Chapman BS, "A region of the 75 kDa neurotrophin receptor homologous to the death domains of TNFR-I and Fas", FEBS Lett, 374, pp.216~220 (1995)
- Dobrowsky RT, "Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor", Science, 265, pp.1596~1599 (1994)
- Casaccia-Bonnefil P, "Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75", Nature, 383, pp.716~719 (1996)
- Micera A, "Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair", Proc Natl Acad Sci, pp.6162~6167 (2001)
- Micera A, "New insights on the involvement of Nerve Growth Factor in allergic inflammation and fibrosis", Cytokine Growth Factor Rev, 14, pp.369~374 (2003)
- Oelmann E, "Nerve growth factor stimulates clonal growth of human lung cancer cell lines and a human glioblastoma cell line expressing high-affinity nerve growth factor binding sites involving tyrosine kinase signaling", Cancer Res, 55, pp.2212~2219 (1995)
- McGregor LM, "Roles of trk family neurotrophin receptors in medullary thyroid carcinoma development and progression", Proc Natl Acad Sci, pp.4540~4545 (1999)
- Pflug BR, "Reduced expression of the low affinity nerve growth factor receptor in benign and malignant human prostate tissue and loss of expression in four human metastatic prostate tumor cell lines", Cancer Res, 52, pp.5403~5406 (1992)
- Descamps S, "Nerve growth factor is mitogenic for cancerous but not normal human breast epithelial cells", J Biol Chem, 273, pp.16659~16662 (1998)
- Bosch FX, "Epidemiology of hepatocellular carcinoma", Clin Liver Dis, 9, pp.191~211 (2005)
- Tang ZY, "Hepatocellular carcinoma: cause, treatment and metastasis", World J Gastroenterol, 7, pp.445~454 (2001)
- Kishibe K, "Production of nerve growth factor by mouse hepatocellular carcinoma cells and expression of TrkA in tumor-associated arteries in mice", Gastroenterology, 122, pp.1978~1986 (2002)
- Oakley F, "Hepatocytes express nerve growth factor during liver injury: evidence for paracrine regulation of hepatic stellate cell apoptosis", Am J Pathol, 163, pp.1849~1858 (2003)
- Cassiman D, "Human and rat hepatic stellate cells express neurotrophins and neurotrophin receptors", Hepatology, 33, pp.148~158 (2001)
- Edmondson H, "Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies", Cancer, 7, pp.462~503 (1954)
- MacSween RN, "Developmental anatomy and normal structure. in: Pathology of the liver", pp.1~49 (1994), Churchill Livingstone
- Dhillon AP, "Immunohistochemical studies on the innervation of human transplanted liver", J Pathol, 167, pp.211~216 (1992)
- Descamps S, "Nerve growth factor stimulates proliferation and survival of human breast cancer cells through two distinct signaling pathways", J Biol Chem, 276, pp.17864~17870 (2001)
- Niederhauser O, "NGF ligand alters NGF signaling via p75(NTR) and trkA", J Neurosci Res, 61, pp.263~272 (2000)
- Dalal R, "Molecular characterization of neurotrophin expression and the corresponding tropomyosin receptor kinases (trks) in epithelial and stromal cells of the human prostate", Mol Cell Endocrinol, 134, pp.15~22 (1997)
- Zhu ZW, "Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells", Clin Cancer Res, 7, pp.105~112 (2001)
- Missale C, "Nerve growth factor abrogates the tumorigenicity of human small cell lung cancer cell lines", Proc Natl Acad Sci, pp.5366~5371 (1998)
- Rasi G, "Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma", World J Gastroenterol, 13, pp.4986~4995 (2007)
- Yuanlong H, "The inhibitory effect of p75 neurotrophin receptor on growth of human hepatocellular carcinoma cells", Cancer Lett, 268, pp.110~119 (2008)
