Article

Nerve growth and expression of receptors for nerve growth factor in tumors of melanocyte origin.

Wistar Institute, Filadelfia, Pennsylvania, United States
Journal of Investigative Dermatology (Impact Factor: 6.37). 06/1991; 96(5):662-5. DOI: 10.1111/1523-1747.ep12470585
Source: PubMed

ABSTRACT Nerve growth factor (NGF) stimulates growth and differentiation of sensory and sympathetic neurons. It is not known what role NGF plays in melanoma development, but nevus and malignant melanoma cells express NGF-receptor (NGF-R). We counted nerve fibers within melanocytic nevi, primary cutaneous melanomas, and cutaneous melanoma metastases using a monoclonal antibody (MoAb) as marker against a 200-kD glycoprotein that is expressed on human nerves. The expression of NGF-R was studied in serial cryostat sections using a MoAb against the NGF-R. Compared to normal skin, increased numbers of nerve fibers were found in 72 melanocytic nevi. In congenital nevi their number significantly increased with age. In 47 primary cutaneous melanomas the number of nerve fibers decreased in proportion to tumor thickness. In 33 cutaneous melanoma metastases no accumulation of nerve fibers was found. NGF-R was not expressed in normal skin melanocytes and in the majority of nevus cells in melanocytic nevi. Considerable numbers of NGF-R-positive nervus cells were found only in some congenital nevi and few acquired nevi with dysplastic features. By contrast, in primary and metastatic melanomas higher expression of NGF-R was observed. The increased number of nerve fibers in melanocytic nevi suggests that neurite-promoting factors are produced in situ. Production of such factors appears to be lost in malignant melanoma cells. The finding of an inverse correlation between an abundance of nerve fibers in NGF-R-poor nevi and a high expression of NGF-R in melanomas that show no evidence of nerve growth suggest a role of NGF and its receptor in malignant melanocytic tumors.

0 Bookmarks
 · 
39 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neural crest cells (NCC) are migratory multipotent cells that give rise to diverse derivatives. They generate various cell types during embryonic development, including neurons and glial cells of the peripheral sensory and autonomic ganglia, Schwann cells, melanocytes, endocrine cells, smooth muscle, and skeletal and connective tissue cells of the craniofacial complex. The multipotency of NCC is thought to be transient at the early stage of NCC generation; once NCC emerge from the neural tube, they change into lineage-restricted precursors. Although many studies have described the clear segregation of NCC lineages right after their delamination from the neural tube, recent reports suggest that multipotent neural crest stem cells (NCSC) are present not only in migrating NCC in the embryo, but also in their target tissues in the fetus and adult. Furthermore, fully differentiated NCC-derived cells such as glial cells and melanocytes have been shown to dedifferentiate or transdifferentiate into other NCC derivatives. The multipotency of migratory and postmigratory NCC-derived cells was found to be similar to that of NCSC. Collectively, these findings support the multipotency or plasticity of NCC and NCC-derived cells. © 2015 Elsevier Inc. All rights reserved.
    Current Topics in Developmental Biology 01/2015; 111:69-95. DOI:10.1016/bs.ctdb.2014.11.003 · 4.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer.
    12/2011; 3(1):510-30. DOI:10.3390/cancers3010510
    This article is viewable in ResearchGate's enriched format