Nerve growth factor and neural oncology

Abstract

The precise role of the nerve growth factor protein (NGF) during the growth and development of the human nervous system is not determined. Although it appears to influence a number of neural functions, its mechanism of action is poorly understood. A number of researchers have proposed that NGF may be involved in several pathological conditions including cancer. It has been shown that NGF is secreted by certain sarcoma (23), neuroblastoma (113), and glioma (7,102,136) cell lines and can bind to neuroblastoma and metastatic melanoma cell lines (42). Neuroblastoma (136,181) and pheochromocytoma (165) cells in vitro can be induced by NGF to differentiate toward a morphologically "more benign" state and appropriate NGF treatment of rats can reduce the number of chemically induced gliomas and neurinomas (174,178). NGF can also reduce the growth of intracerebrally inoculated anaplastic glioma cells (172). Anti-NGF treatment of rats (178) and mice (179) can alter the tumor distribution observed following ethylnitrosourea or benzo(a)pyrene treatment (10). In humans, it has been reported that serum levels of NGF are usually elevated in persons "at risk" for neurofibromatosis (156). The precise nature of the NGF role is not known in these instances. Further understanding of the action of NGF could be of clinical importance.

Characterization of functional nerve growth factor‐receptors in a CNS glial cell line: Monoclonal antibody 217c recognizes the nerve growth factor‐receptor on C6 glioma cells

“…In C6 cells, anaplastic F98 glioma cells (Vinores, 1983), ethylnitrosourea-induced CNS tumors (Vinores and Perez-Polo, 1983), and in the various neural tumor cells described earlier that contain the high-affinity NGF-R including SW707 colo-rectal carcinoma cells (Rakowicz-Szulczynska et al, 1988), a common consequence of NGF treatment is the cessation of cell proliferation. The control of proliferation may result from a balance between stimulatory and inhibitory factors, as there is between NGF vs. EGF in PC12 cells (Boonstra ct al., 1987;Lazarovici et al, 1987), and NGF vs. PDGF in SW707 colo-rectal cells (Rakowicz-Szulczynska and Koprowski, 1989).…”

Neurotrophic Effects of Mu Bie Zi (Momordica cochinchinensis) Seed Elucidated by High-Throughput Screening of Natural Products for NGF Mimetic Effects in PC-12 Cells

“…While most drug regimens have capacity to improve quality of life, they do not address the underlying etiology of the disease and thereby do not arrest progression degenerative processes. Although endogenous synthesis of trophic molecules such as nerve growth factor (NGF) [1], brain-derived neurotrophic factor (BDNF) and neurotrophin-3/neurotrophin-4 can effectively stimulate neuronal growth/repair [2, 3], therapeutic applications are limited by a wide range of negative side effects such as neuropathic pain [4, 5], bladder/urinary pain [6], itchy skin (pruritus) atopic dermatitis [7 – 9], deep tissue tenderness [10, 11], exacerbated inflammatory conditions such as arthritis, asthma [10, 12, 13], inter-vertebral disc degeneration [14] and cancer [15 – 17]. Furthermore, elevated levels of NGF in various neuronal tissue can lead to behavioral/cognitive disorders such as autism [18], bipolar [19] and attention deficit/hyperactivity disorder.…”

NGF Blockade at Early Times during Bone Cancer Development Attenuates Bone Destruction and Increases Limb Use

“…Extensive in vitro studies show that NGF and/or TrkA drive the growth and metastasis of breast, ovarian, lung, pancreas, and prostate tumor cells (18-20). Moreover, in vivo studies show that anti-NGF inhibits ethylnitrosourea-induced carcinogenesis in mice and rats (21), and either anti-NGF or siRNA against NGF inhibits breast cancer tumor growth and metastasis in a mouse xenograft model (22). …”