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Expression of NGF/proNGF and Their Receptors TrkA, p75<sup>NTR</sup> and Sortilin in Melanoma
oleh: Mark Marsland, Amiee Dowdell, Chen Chen Jiang, James S. Wilmott, Richard A. Scolyer, Xu Dong Zhang, Hubert Hondermarck, Sam Faulkner
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2022-04-01 |
Deskripsi
There is increasing evidence that nerve growth factor (NGF) and its receptors, the neurotrophic receptor tyrosine kinase 1 (NTRK1/TrkA), the common neurotrophin receptor (NGFR/p75<sup>NTR</sup>) and the membrane receptor sortilin, participate in cancer growth. In melanoma, there have been some reports suggesting that NGF, TrkA and p75<sup>NTR</sup> are dysregulated, but the expression of the NGF precursor (proNGF) and its membrane receptor sortilin is unknown. In this study, we investigated the expression of NGF, proNGF, TrkA, p75<sup>NTR</sup> and sortilin by immunohistochemistry in a series of human tissue samples (<i>n</i> = 100), including non-cancerous nevi (<i>n</i> = 20), primary melanomas (<i>n</i> = 40), lymph node metastases (<i>n</i> = 20) and distant metastases (<i>n</i> = 20). Immunostaining was digitally quantified and revealed NGF and proNGF were expressed in all nevi and primary melanomas, and that the level of expression decreased from primary tumors to melanoma metastases (<i>p</i> = 0.0179 and <i>p</i> < 0.0001, respectively). Interestingly, TrkA protein expression was high in nevi and thin primary tumors but was strongly downregulated in thick primary tumors (<i>p</i> < 0.0001) and metastases (<i>p</i> < 0.0001). While p75<sup>NTR</sup> and sortilin were both expressed in most nevi and melanomas, there was no significant difference in expression between them. Together, these results pointed to a downregulation of NGF/ProNGF and TrkA in melanoma, and thus did not provide evidence to support the use of anti-proNGF/NGF or anti-TrkA therapies in advanced and metastatic forms of melanoma.