Nerve growth factor and its receptor tyrosine kinase TrkA are overexpressed in cervical squamous cell carcinoma

FASEB BioAdvances

Marjorie M. Walker¹  Sonia M. Oliveira¹  Christopher W. Rowe¹  Phillip Jobling²  Hubert Hondermarck²  Nathan Griffin²  Sam Faulkner²  Janine M. Lombard³ 

[1] Hunter Medical Research Institute University of Newcastle New Lambton NSW Australia;School of Biomedical Sciences and Pharmacy Faculty of Health and Medicine University of Newcastle Callaghan NSW Australia;School of Medicine and Public Health Faculty of Health and Medicine University of Newcastle Callaghan NSW Australia;

关键词: cervical cancer;    nerves;    NGF;    p75NTR;    proNGF;    sortilin;   

DOI  :  10.1096/fba.2020-00016

来源: DOAJ

【 摘 要 】

Abstract Nerve growth factor (NGF) and its receptors are increasingly implicated in cancer progression, but their expression in cervical cancer is unclear. The objective of this study was to define the protein expression of NGF, its precursor (proNGF), as well as their receptors, the tyrosine kinase receptor TrkA, the common neurotrophin receptor p75NTR and the pro‐neurotrophin receptor sortilin in cervical cancer. Immunohistochemistry was performed in a cohort of cervical cancers (n = 287), including the two major subtypes of the disease: squamous cell carcinomas (SCC) and adenocarcinomas (AC). Normal cervical tissues (n = 28) were also analyzed. Protein expression was determined by computer‐based digital quantification of staining intensity and comparative statistical analyses were made with clinicopathological parameters including histological subtype, age, grade, tumor size, lymph node invasion, and stage. The expression of NGF, proNGF, TrkA, p75NTR, and sortilin was higher in cervical cancer compared to normal cervical tissues. NGF and TrkA were found overexpressed in SCC compared to AC (P = .0006 and P < .0001, respectively). The expression of NGF (P = .0053), proNGF (P = .0022), and p75NTR (P = .0002), but not that of TrkA or sortilin, was associated with increasing grade in SCC. In addition, nerve infiltration into the tumor microenvironment was assessed using the pan‐neuronal marker PGP9.5. Infiltrating nerves were detected in 27% of cervical tumors and expressed TrkA. Functional investigations using the HELA cervical cancer cell line indicated that the Trk tyrosine kinase inhibitor GNF‐5837 reduced cell viability through decreased ERK1/2 activation. Together, these data reveal the overexpression of NGF and TrkA in cervical SCC, suggesting a potential therapeutic value of targeting the NGF‐TrkA signaling pathway in this subtype of cervical cancer.

【 授权许可】

Unknown