Chordoma Foundation

NGF

Nerve Growth Factor is a growth factor and a signaling molecule that binds to two distinct receptors.

Receptors:TrkA and p75
Location: NGF at 1p13

Binding of NGF
to TrkA promotes cell survival. Binding to p75, on the other hand, triggers apoptosis. If TrkA and p75 are both expressed, NGF-TrkA signaling overrides NGF-p75 signaling and cells survive. NGF’s role in determining whether cell survive or die have been shown to play a role in tumor cells for various malignancies.1

NGF in Chordoma

Because NGF has been shown to have effects on the proliferation and survival of tumor cells in other cancers (including breast cancer, rhabdomyosarcoma, and pheochromocytoma),1 chordoma researchers have begun to explore the role of NGF and its receptors in chordoma tumor cells. Studies have uncovered chromosomal abnormalities involving NGF and have shown that NGF and its receptors are expressed. However, further research will be necessary to understand NGF signling in chordoma and to evaluate whether it could be targeted as a method for treating the disease.

Molecular Evidence


Copy Number Variation

Chromosomal Aberrations: Losses of the region of chromosome 1 where the NGF gene resides, or of chromosome 1 in its entirety, are common chromosomal aberrations observed in chordomas.2 3 4 5

Protein Expression

Mean expression of NGF and of the TrkA receptor is higher in chordoma cells than in notochord cells, while expression of the p75 receptor is similar in the cell types. This suggests that chordoma cell survival is favored over apoptosis, and indeed, quantitative measures revealed that the mean potential proliferation index was higher in chordoma cells than in notochord cells and the apoptosis index was lower.1


References

1.
Park J, Lee C, Koh J, Lee J, Park E, Riew K. Overexpressions of nerve growth factor and its tropomyosin-related kinase A receptor on chordoma cells. Spine (Phila Pa 1976). 2007;32(18):1969-1973. [PubMed]
2.
Scheil S, Brüderlein S, Liehr T, et al. Genome-wide analysis of sixteen chordomas by comparative genomic hybridization and cytogenetics of the first human chordoma cell line, U-CH1. Genes Chromosomes Cancer. 2001;32(3):203-211. [PubMed]
3.
Rinner B, Weinhaeusel A, Lohberger B, et al. Chordoma characterization of significant changes of the DNA methylation pattern. PLoS One. 2013;8(3):e56609. [PubMed]
4.
Le L, Nielsen G, Rosenberg A, et al. Recurrent chromosomal copy number alterations in sporadic chordomas. PLoS One. 2011;6(5):e18846. [PubMed]
5.
Hallor K, Staaf J, Jönsson G, et al. Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation. Br J Cancer. 2008;98(2):434-442. [PubMed]