Pigment Cell & Melanoma Research最新文献

{"title":"Effects of EGFR-TKI on epidermal melanin unit integrity: Therapeutic implications for hypopigmented skin disorders","authors":"Ping Xu,&nbsp;Lingli Yang,&nbsp;Sylvia Lai,&nbsp;Fei Yang,&nbsp;Yasutaka Kuroda,&nbsp;Huimin Zhang,&nbsp;Daisuke Tsuruta,&nbsp;Ichiro Katayama","doi":"10.1111/pcmr.13171","DOIUrl":"10.1111/pcmr.13171","url":null,"abstract":"<p>Epidermal melanin unit integrity is crucial for skin homeostasis and pigmentation. Epidermal growth factor (EGF) receptor (EGFR) is a pivotal player in cell growth, wound healing, and maintaining skin homeostasis. However, its influence on skin pigmentation is relatively unexplored. This study investigates the impact and underlying mechanisms of EGFR inhibitors on skin pigmentation. We evaluated EGF and EGFR expression in various skin cells using quantitative real-time PCR, Western blot, and immunofluorescence. EGF and EGFR were predominantly expressed in epidermal keratinocytes, and treatment with the EGFR tyrosine kinase inhibitors (EGFR-TKIs) gefitinib and PD153035 significantly increased stem cell factor (SCF) and endothelin-1 (ET-1) expression in cultured keratinocytes. Enhanced melanocyte migration and proliferation were observed in co-culture, as evidenced by time-lapse live imaging and single-cell tracking assays. Furthermore, topical application of gefitinib to guinea pig dorsal skin induced increased pigmentation and demonstrated efficacy in mitigating rhododendrol-induced leukoderma. Suppression of EGF signaling indirectly enhanced skin pigmentation by upregulating SCF and ET-1 in epidermal keratinocytes. This novel mechanism highlights the pivotal role of EGF signaling in regulating skin pigmentation, and topical EGFR-TKI therapy at an appropriate dose may be a promising approach for depigmentation disorder management.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"514-529"},"PeriodicalIF":4.3,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis reveals inflammatory biomarkers for skin melanoma prognosis","authors":"Zhi-Qing Zhan,&nbsp;Jia-Xin Li,&nbsp;Xin-Lei Hu","doi":"10.1111/pcmr.13172","DOIUrl":"10.1111/pcmr.13172","url":null,"abstract":"","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"510-513"},"PeriodicalIF":4.3,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140833859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"25th International Pigment Cell Conference, Bilbao, Spain IPCC 2023","authors":"","doi":"10.1111/pcmr.13145","DOIUrl":"10.1111/pcmr.13145","url":null,"abstract":"","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 5","pages":"597-655"},"PeriodicalIF":3.9,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA M6A modification shaping cutaneous melanoma tumor microenvironment and predicting immunotherapy response","authors":"Yanhong Wu,&nbsp;Hongying He,&nbsp;Kairong Zheng,&nbsp;Zhenxin Qin,&nbsp;Naikun Cai,&nbsp;Shuguang Zuo,&nbsp;Xiao Zhu","doi":"10.1111/pcmr.13170","DOIUrl":"10.1111/pcmr.13170","url":null,"abstract":"<p>Recent years have seen rising mortality rates linked to cutaneous melanoma (SKCM), despite advances in immunotherapy. Understanding RNA N6-methyladenosine (M6A) significance in SKCM is crucial for prognosis, tumor microenvironment (TME), immune cell presence, and immunotherapy efficacy. We analyzed 23 M6A regulators using SKCM samples from TCGA and GEO databases, identifying three M6A modification patterns linked to TME cell infiltration. Principal component analysis (PCA) yielded an M6A score for individual tumors, utilizing patient gene expression profiles and CNV data from TCGA. M6A modification patterns play a crucial role in SKCM development and progression, influencing tumor attributes such as inflammatory stage, subtype, TME interstitial activity, and genetic mutations. The M6A score independently predicts patient outcomes and correlates with improved response to immunotherapy, validated across anti-PD-1 and anti-PD-L1 therapy cohorts. M6A modifications significantly impact the TME landscape, with the M6A score serving as a predictive marker for immunotherapy response. Integrating M6A-related information into clinical practice could revolutionize SKCM management and treatment strategies.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"496-509"},"PeriodicalIF":4.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular heterogeneity of quiescent melanocyte stem cells revealed by single-cell RNA-sequencing","authors":"Joseph W. Palmer,&nbsp;Nilesh Kumar,&nbsp;Luye An,&nbsp;Andrew C. White,&nbsp;M. Shahid Mukhtar,&nbsp;Melissa L. Harris","doi":"10.1111/pcmr.13169","DOIUrl":"10.1111/pcmr.13169","url":null,"abstract":"<p>Melanocyte stem cells (McSCs) of the hair follicle are a rare cell population within the skin and are notably underrepresented in whole-skin, single-cell RNA sequencing (scRNA-seq) datasets. Using a cell enrichment strategy to isolate KIT+/CD45− cells from the telogen skin of adult female C57BL/6J mice, we evaluated the transcriptional landscape of quiescent McSCs (qMcSCs) at high resolution. Through this evaluation, we confirmed existing molecular signatures for qMcCS subpopulations (e.g., <i>Kit+</i>, <i>Cd34+/−</i>, <i>Plp1+</i>, <i>Cd274+/−</i>, <i>Thy1+</i>, <i>Cdh3+/−</i>) and identified novel qMcSC subpopulations, including two that differentially regulate their immune privilege status. Within qMcSC subpopulations, we also predicted melanocyte differentiation potential, neural crest potential, and quiescence depth. Taken together, the results demonstrate that the qMcSC population is heterogeneous and future studies focused on investigating changes in qMcSCs should consider changes in subpopulation composition.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"480-495"},"PeriodicalIF":4.3,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-Mercaptonicotinoyl glycine, a new potent melanogenesis inhibitor, exhibits a unique mode of action while preserving melanocyte integrity","authors":"Peggy Sextius,&nbsp;Emilie Warrick,&nbsp;Amélie Prévot-Guéguiniat,&nbsp;Guillaume Lereaux,&nbsp;Florence Boirre,&nbsp;Ludwig Baux,&nbsp;Safa Ben Hassine,&nbsp;Jie Qiu,&nbsp;Xiaoming Huang,&nbsp;Jinzhu Xu,&nbsp;Sébastien Grégoire,&nbsp;Shosuke Ito,&nbsp;Kazumasa Wakamatsu,&nbsp;Xavier Marat","doi":"10.1111/pcmr.13168","DOIUrl":"10.1111/pcmr.13168","url":null,"abstract":"<p>Research on new ingredients that can prevent excessive melanin production in the skin while considering efficacy, safety but also environmental impact is of great importance to significantly improve the profile of existing actives on the market and avoid undesirable side effects. Here, the discovery of an innovative technology for the management of hyperpigmentation is described. High-throughput screening tests on a wide chemical diversity of molecules and in silico predictive methodologies were essential to design an original thiopyridinone backbone and select 2-mercaptonicotinoyl glycine (2-MNG) as exhibiting the most favorable balance between the impact on water footprint, skin penetration potential and performance. The effectiveness of 2-MNG was confirmed by topical application on pigmented reconstructed epidermis and human skin explants. In addition, experiments have shown that unlike most melanogenesis inhibitors on the market, this molecule is not a tyrosinase inhibitor. 2-MNG binds to certain melanin precursors, preventing their integration into growing melanin and leading to inhibition of eumelanin and pheomelanin synthesis, without compromising the integrity of melanocytes.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"462-479"},"PeriodicalIF":4.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma","authors":"Stephan Forchhammer,&nbsp;Valentin Aebischer,&nbsp;Daniela Lenders,&nbsp;Christian M. Seitz,&nbsp;Christopher Schroeder,&nbsp;Alexandra Liebmann,&nbsp;Michael Abele,&nbsp;Hannah Wild,&nbsp;Ewa Bien,&nbsp;Malgorzata Krawczyk,&nbsp;Dominik T. Schneider,&nbsp;Ines B. Brecht,&nbsp;Lukas Flatz,&nbsp;Matthias Hahn","doi":"10.1111/pcmr.13167","DOIUrl":"10.1111/pcmr.13167","url":null,"abstract":"<p>Pediatric melanomas are rare tumors that have clinical and histological differences from adult melanomas. In adult melanoma, the immunohistochemical marker PRAME is increasingly employed as a diagnostic adjunct. PRAME is also under investigation as a target structure for next-generation immunotherapies including T-cell engagers. Little is known about the characteristics of PRAME expression in pediatric melanoma. In this retrospective study, samples from 25 pediatric melanomas were compared with control groups of melanomas in young adults (18–30 years; <i>n</i> = 32), adult melanoma (&gt;30 years, <i>n</i> = 30), and benign melanocytic nevi in children (0–18 years; <i>n</i> = 30) with regard to the immunohistochemical expression of PRAME (diffuse PRAME expression &gt;75%/absolute expression). Pediatric melanomas show lower diffuse PRAME expression (4%) and lower absolute PRAME expression (25%) compared to young adult melanomas (15.6%/46.8%) and adult melanomas (50%/70%). A significant age-dependent expression could be observed. An analysis of event-free survival shows no prognostic role for PRAME in pediatric melanoma and young adult melanoma, but a significant association with diffuse PRAME expression in adulthood. The age dependency of PRAME expression poses a potential pitfall in the diagnostic application of melanocytic tumors in young patients and may limit therapeutic options within this age group. The immunohistochemical expression of the tumor-associated antigen PRAME is an increasingly important diagnostic marker for melanocytic tumors and is gaining attention as a possible immunotherapeutic target in melanoma. As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age-dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"453-461"},"PeriodicalIF":4.3,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The metabolism of melanin synthesis—From melanocytes to melanoma","authors":"Marelize Snyman,&nbsp;Rachel Elizabeth Walsdorf,&nbsp;Sophia Nicole Wix,&nbsp;Jennifer Gibson Gill","doi":"10.1111/pcmr.13165","DOIUrl":"10.1111/pcmr.13165","url":null,"abstract":"<p>Melanin synthesis involves the successful coordination of metabolic pathways across multiple intracellular compartments including the melanosome, mitochondria, ER/Golgi, and cytoplasm. While pigment production offers a communal protection from UV damage, the process also requires anabolic and redox demands that must be carefully managed by melanocytes. In this report we provide an updated review on melanin metabolism, including recent data leveraging new techniques, and technologies in the field of metabolism. We also discuss the many aspects of melanin synthesis that intersect with metabolic pathways known to impact melanoma phenotypes and behavior. By reviewing the metabolism of melanin synthesis, we hope to highlight outstanding questions and opportunities for future research that could improve patient outcomes in pigmentary and oncologic disease settings.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"438-452"},"PeriodicalIF":4.3,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic insights into Tietz albinism-deafness syndrome: A new dominant-negative mutation in MITF","authors":"Kohei Yamamoto,&nbsp;Ken Okamura,&nbsp;Kazumasa Wakamatsu,&nbsp;Shosuke Ito,&nbsp;Kozue Akabane,&nbsp;Yosuke Arai,&nbsp;Junnosuke Kawaguchi,&nbsp;Yutaka Hozumi,&nbsp;Tamio Suzuki","doi":"10.1111/pcmr.13166","DOIUrl":"10.1111/pcmr.13166","url":null,"abstract":"<p>Tietz albinism-deafness syndrome (TADS) is a rare and severe manifestation of Waardenburg syndrome that is primarily linked to mutations in <i>MITF</i>. In this report, we present a case of TADS resulting from a novel c.637G&gt;C mutation in <i>MITF</i> (p.Glu213Gln; GenBank Accession number: NM_000248). A 3-year-old girl presented with congenital generalized hypopigmentation of the hair, skin, and irides along with complete sensorineural hearing loss. Histopathological and electron microscopy investigations indicated that this variant did not alter the number of melanocytes in the skin but significantly impaired melanosome maturation within melanocytes. Comprehensive melanin analysis revealed marked reductions in both eumelanin (EM) and pheomelanin (PM) rather than changes in the EM-to-PM ratio observed in oculocutaneous albinism. We conducted an electrophoretic mobility shift assay to investigate the binding capability of the identified variant to DNA sequences containing the E-box motif along with other known variants (p.Arg217del and p.Glu213Asp). Remarkably, all three variants exhibited dominant-negative effects, thus providing novel insights into the pathogenesis of TADS. This study sheds light on the genetic mechanisms underlying TADS and offers a deeper understanding of this rare condition and its associated mutations in <i>MITF</i>.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"430-437"},"PeriodicalIF":4.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical antibiotics limit depigmentation in a mouse model of vitiligo","authors":"Ahmed Ahmed Touni,&nbsp;Rachel Sohn,&nbsp;Cormac Cosgrove,&nbsp;Rohan S. Shivde,&nbsp;Emilia R. Dellacecca,&nbsp;Rasha T. A. Abdel-Aziz,&nbsp;Kettil Cedercreutz,&nbsp;Stefan J. Green,&nbsp;Hossam Abdel-Wahab,&nbsp;I. Caroline Le Poole","doi":"10.1111/pcmr.13164","DOIUrl":"10.1111/pcmr.13164","url":null,"abstract":"<p>Oral neomycin administration impacts the gut microbiome and delays vitiligo development in mice, and topical antibiotics may likewise allow the microbiome to preserve skin health and delay depigmentation. Here, we examined the effects of 6-week topical antibiotic treatment on vitiligo-prone pmel-1 mice. Bacitracin, Neosporin, or Vaseline were applied to one denuded flank, while the contralateral flank was treated with Vaseline in all mice. Ventral depigmentation was quantified weekly. We found that topical Neosporin treatment significantly reduced depigmentation and exhibited effects beyond the treated area, while Bacitracin ointment had no effect. Stool samples collected from four representative mice/group during treatment revealed that Neosporin treatment aligned with reduced abundance of the <i>Alistipes</i> genus in the gut, while relevant changes to the skin microbiome at end point were less apparent. Either antibiotic treatment led to reduced expression of MR1, potentially limiting mucosal-associated invariant T-cell activation, while Neosporin-treated skin selectively revealed significantly reduced CD8+ T-cell abundance. The latter finding aligned with reduced expression of multiple inflammatory markers and markedly increased regulatory T-cell density. Our studies on favorable skin and oral antibiotic treatment share the neomycin compound, and in either case, microbial changes were most apparent in stool samples. Taken together, neomycin-containing antibiotic applications can mediate skin Treg infiltration to limit vitiligo development. Our study highlights the therapeutic potential of short-term antibiotic applications to limit depigmentation vitiligo.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 5","pages":"583-596"},"PeriodicalIF":3.9,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}