Year: 2007
Type: article
Abstract: For the vast majority of cancers at least some progress in effective treatment has been forthcoming over the years. Not so for melanoma. This highly aggressive and increasingly common cancer can be cured by surgical excision at an early stage, but metastatic melanoma remains highly refractive to therapy. It is increasingly clear that melanoma is a complex disease in which pathways critical for melanocyte development have been subverted to promote proliferation, and that the normal pro-senescence mechanisms that defend us against cancer progression have been suppressed. In recent years significant breakthroughs have been made in identifying the genetic lesions that underpin the genesis of melanoma, most notably those that lead to activation of BRAF or NRAS and suppression of the Rb1 pathway. Yet, as highlighted in the review from Tanja Rothhammer and Anja Bosserhoff, the contribution of epigenetic changes, in which alterations in chromatin organization and modification as well as DNA-methylation patterns affect gene expression without alterations to the DNA sequence, is increasingly recognized as a significant factor in disease progression. The catalogue of known epigenetic modifications in melanoma and potential strategies directed towards modifying the melanoma epigenome are discussed. Although there is an urgent need for novel and effective therapeutic strategies for melanoma, equally important is the ability to detect and identify metastatic and metastasising melanoma cells. This may not be as straightforward as it might seem. While more differentiated, pigmented lesions my be readily detected, what markers will be effective for melanoma cells circulating in the bloodstream, an indicator of metastatic disease that may not be immediately apparent. The current repertoire of melanoma markers includes the microphthalmia-associated transcription factor, Mitf, and a range of proteins produced from genes that are Mitf targets, such as tyrosinase and melan-a. Yet increasing evidence suggests that melanomas may generate melanoma ‘stem cells’ and that these may be Mitf-negative and therefore, like natural melanocyte stem cells, lack all common markers of the melanocyte lineage. In the future it will be imperative to generate markers that will detect such melanoma stem cells, but for now the advantages and disadvantages of the wide range of melanoma markers currently in use are comprehensively reviewed by Melanie Ziman. For a long time role of calcium in signalling in pigment cells has received perhaps less attention that it deserves. The results presented in the paper from Bush and Simon highlight the fact that melanin has the potential to bind calcium with an affinity that would be consistent with it performing a key role in regulating calcium homeostasis in the cell. Several recent papers have highlighted the key role played by calcium within pigment cells, in melanosome transport for example, or the interesting work on the golden gene slc24a5, that appears to be a melanosome-associated ion exchanger implicated in uptake of calcium into the melanosome. Given the phenotype of zebrafish bearing golden mutations and the potential of this gene for regulation of human pigmentation, an interesting question arising from the Bush and Simon paper is whether intra-melanosome calcium levels might also play major role in signalling to the cell that a mature melanosome has been formed. One of the delights of being Editor-in-Chief of Pigment Cell Research is that I get to choose the cover for each issue. Usually the cover image is provided by a member of the scientific community and frequently represents a striking immunofluorescence image of pigment cells in culture or during development. Occasionally the cover shows the natural pigmentation pattern of a wild animal, the image provided by Rich Spritz of the cheetah in the Masai Mara on the cover of the December issue for example. But the deserved winner of the 2006 cover image of the year this time is not a scientist, but an artist: Pascale Pollier, who designed and made the melanocyte sculpture that graced the October cover. This remarkable piece of work caught the imagination of the voters and received twice as many votes as the next most popular image, the cheetah. It is a just reward for an artist who invested many months in bringing this beautiful fusion of art and science to fruition. For once the usual prize, a year's free subscription to the journal seems inappropriate. Instead I have asked Pascale to produce another cover image and use her talent as an artist to depict the intrinsic splendour of pigment cells. Art and science usually lead independent existences, but of all cell types, it seems to me that the pigment cell that brings so much beauty to life, seems most suited to bridging the chasm that runs between art and science. It is with great sadness that I bring to the attention of all interested in pigmentation and pigment cells, the deaths of two pioneers in the world of pigment cell biology: Mac Hadley, a pioneer in the field of melanocortins, shockingly murdered in his own home in Arizona by a burglar; and Aaron Lerner, who discovered melantonin and MSH, who died suddenly of a heart attack aged 87 a short time ago. We all are indebted to their contribution to pigment cell biology and I anticipate publishing obituaries for both in an upcoming issue of this journal.
Source: Pigment Cell Research
Author: Colin Goding
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2083164089