Transient lysosomal activation is essential for p75 nerve growth factor receptor expression in myelinated Schwann cells during Wallerian degeneration / 대한해부학회지

Myelinated Schwann cells in the peripheral nervous system express the p75 nerve growth factor receptor (p75NGFR) as a consequence of Schwann cell dedifferentiation during Wallerian degeneration. p75NGFR has been implicated in the remyelination of regenerating nerves. Although many studies have shown various mechanisms underlying Schwann cell dedifferentiation, the molecular mechanism contributing to the re-expression of p75NGFR in differentiated Schwann cells is largely unknown. In the present study, we found that lysosomes were transiently activated in Schwann cells after nerve injury and that the inhibition of lysosomal activation by chloroquine or lysosomal acidification inhibitors prevented p75NGFR expression at the mRNA transcriptional level in an ex vivo Wallerian degeneration model. Lysosomal acidification inhibitors suppressed demyelination, but not axonal degeneration, thereby suggesting that demyelination mediated by lysosomes may be an important signal for inducing p75NGFR expression. Tumor necrosis factor-alpha (TNF-alpha) has been suggested to be involved in regulating p75NGFR expression in Schwann cells. In this study, we found that removing TNF-alpha in vivo did not significantly suppress the induction of both lysosomes and p75NGFR. Thus, these findings suggest that lysosomal activation is tightly correlated with the induction of p75NGFR in demyelinating Schwann cells during Wallerian degeneration.

Expression of nerve growth factor and nerve growth factor receptor in human pancreatic cancer and its clinical significance / 第二军医大学学报

Objective: To explore the expression of nerve growth factor (NGF), its receptor P75NGFR and TrkA in the human pancreatic cancer tissues, and to study the relationship between the expression and clinical-pathological indices. Methods: The expression and morphological distribution of NGF, P75NGFR and TrkA were investgated in 65 pancreatic cancer tissues and 18 normal pancreas and chronic pancreatitis tissues by means of immunohistochemistry; the relationship between the expression and clinical-pathological indices was also investigated. Results: The expression of NGF and TrkA in human pancreatic cancer tissues was higher than that in the normal pancreas and chronic pancreatitis. Expression of P75NGFR had no significant change in the two groups. The expression of NGF was positively correlated with tumor size and was also associated with lymphatic invasion. The expression of P75NGFR and TrkA was closely correlated with lymphatic invasion. We also found that the expression of NGF was correlated with histological differentiation, tumor stage, tumor size and lymphatic invasion; the closest relationship was found between the expression of NGF and tumor size. The expression of P75NGFR was correlated with lymphatic invasion, the expression of TrkA was Correlated with both lymphatic invasion and tumor TNM stage. Patient's prognosis after surgery was mainly correlated with lymphatic invasion and the positive expression of TrkA. Conclusion: NGF, P75NGFR and TrkA participate in the progress of pancreatic cancer. TrkA is closely related to pancreatic cancer and can serve as an important target for gene therapy of pancreatic cancer in the future.

The Expressions of Nerve Growth Factor and Its Receptor p75NGFR in Hepatocellular Carcinoma: Their Relation with the Clinicopathologic Factors

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.