title: Expression of NGF in hepatocellular carcinoma cells with its receptors in non-tumor cell components.
abstract: Nerve growth factor (NGF) is suggested to have a role in tumor progression in addition to its role in differentiation and survival of neuronal cells. We investigated expression of NGF and its receptors, TrkA and p75NTR, in hepatocellular carcinomas (HCCs). Although hepatocytes and hepatic stellate cells (HSCs) showed respectively weak and intense NGF immunostaining in the background livers of patients suffering from liver cirrhosis (LC) or chronic hepatitis (CH), intense staining was demonstrated in HCC cells of 33 of 54 (61.1%) tumors. RT-PCR detected NGF mRNA in 7 freshly-isolated HCC samples, and in 2 of 4 cases, in which both background livers and tumors could be analyzed, NGF mRNA was more abundant in the tumors than the background livers. TrkA was detected in the smooth muscle cells of hepatic arteries, but it was negative in tumor cells as well as non-neoplastic hepatocytes. p75NTR and alpha-smooth muscle actin (alphaSMA) was expressed in HSCs in the background liver and fibroblast-like cells in stromal septa, whereas HSCs within the HCC tissues were mostly negative for p75NTR but positive for alphaSMA. This suggests that HSCs in HCC have a different property from those in background livers. Furthermore, the stromal septa contained abundant nerve fibers, which may be related to the increased NGF expression in HCC cells. NGF and its receptors are then thought to have a role in cellular interactions involving HCC cells, HSCs, arterial cells and nerve cells in HCC tissues.
authors.affiliation: Department of Pathology, Asahikawa Medical College, Asahikawa, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tokusashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Asai
authors.forename: Susumu
authors.initials: S
authors.lastname: Tamakawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Masumi
authors.initials: M
authors.lastname: Yoshie
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yaginuma
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miyokawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Aoki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kino
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kasai
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006521:Hepatitis, Chronic / Q000378:metabolism; D022781:Hepatocytes / Q000737:chemistry*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008113:Liver Neoplasms / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000032:analysis; D017475:Receptors, Nerve Growth Factor / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA