Pigment Cell & Melanoma Research最新文献

Melanin is the primary pigment found in the skin, hair, wool and feathers of many vertebrates and plays a crucial role in determining the physical appearance and physiological performance of livestock species. Melanin functions in thermoregulation as well as coloration, photoprotection, and adaptation to diverse environmental conditions. This review examines the biosynthesis of melanin and the genetics of melanogenesis in major livestock species such as cattle, sheep, goats, pigs, horses, and poultry, and the roles of melanin-based pigmentation within different systems of animal production. The genetic loci (MC1R, ASIP, TYRP1, TYR, PMEL, MITF, KIT, and others) and polygenic modifiers determine the type and intensity of pigment distribution patterns. Melanin also has a variety of ecological roles, or functions, in addition to economically important traits, affecting adaptation to environmental restraints, product quality, and market preferences. Despite major advances in genomic and transcriptomic studies, many questions still remain, especially in the lack of direct experimental evidence, an insufficient understanding of the physiological roles of melanin in livestock, and a lack of functional validation of key pigmentation genes under production conditions. Future research should focus on bridging these gaps and translating this genetic knowledge to breeding strategies.

Mucosal melanoma is a rare, aggressive melanoma subtype arising from melanocytes within mucosal surfaces of the head and neck, anorectal, gastrointestinal, and genitourinary tracts. Unlike ultraviolet-driven cutaneous melanoma, mucosal melanoma has lower tumor mutational burden, fewer BRAF V600 alterations, greater structural genomic complexity, and recurrent drivers including mutations in KIT, NRAS, NF1, SF3B1, and copy-number alterations. It is often diagnosed at advanced stages, recurs locally, disseminates early, and responds less favorably to immune checkpoint inhibition than cutaneous melanoma. Low neoantigen burden contributes to this resistance, but emerging evidence indicates that antitumor immunity is also shaped by spatially organized tumor-immune interactions, site-specific mucosal biology, suppressive myeloid and stromal programs, angiogenic signaling, and underexplored innate checkpoint pathways. Here, we review mucosal melanoma as a biologically distinct model of immune-excluded melanoma, summarizing its clinical behavior, genomic architecture, immunotherapy outcomes, and mechanisms of checkpoint resistance, with emphasis on restricted intratumoral CD8-positive T-cell infiltration, macrophage- and stroma-rich barriers, angiogenic remodeling, and candidate innate checkpoints including B7-H3, CD24–Siglec-10, CD47–SIRPα, and B7-H6/NKp30. We further discuss how spatial and circulating biomarkers may support response-adapted translational studies and define actionable immune states across mucosal melanoma sites.

Vitiligo is an acquired depigmentation disorder characterized by the loss of epidermal melanocytes and can markedly impair patients' quality of life. Because of its dual effects on immunosuppression and repigmentation, UVB phototherapy has become a first-line treatment for vitiligo. It is particularly valuable in inducing repigmentation of skin lesions. Since epidermal melanocytes are markedly reduced or even absent in vitiligo lesions, migration of melanocyte stem cells (McSCs) from the hair follicle bulge to the interfollicular epidermis is considered a critical step in UVB-induced repigmentation, as it enables the replenishment of epidermal melanocytes. Therefore, this review summarizes the molecular mechanisms by which UVB induces McSC migration. Current evidence suggests that UVB primarily regulates McSC migration, proliferation, and differentiation indirectly by remodeling the McSC niche. In this process, keratinocytes, inflammatory cells, and other niche-associated cells release multiple paracrine mediators, including SCF, EDN1, bFGF, PGE2, and WNT. These factors coordinately regulate the physiological activities of McSCs. In addition, we propose that changes in the expression of melanocyte surface receptors may be an important limiting factor governing the migratory response of McSCs. This review also discusses the molecular markers of McSCs and the physiological changes that accompany their migration. Based on current evidence, we further hypothesize that some melanocytes migrating to the epidermis may retain the ability to dedifferentiate and return to the hair follicle. This process may represent an important mechanism by which UVB-induced McSC migration does not deplete the McSC reservoir.

Uveal melanoma (UM) is driven by activating GNAQ/GNA11 mutations, predominantly at the hotspot Q209 residue. However, the functional impact of distinct GNAQ Q209 substitutions on downstream signaling and malignant progression remains unclear. Using immune-competent, multistep UM mouse models combining eye-restricted mutant GNAQ with BAP1 loss and MYC activation, we directly compared GNAQ^Q209L and GNAQ^Q209R in an otherwise matched genetic context. Tumors arising from either allele shared similar histology and cell-state composition. However, GNAQ^Q209L tumors progressed faster and were associated with reduced survival. In contrast, GNAQ^Q209R tumor-derived cell lines exhibited greater ex vivo fitness (proliferation, clonogenicity, and migration), whereas GNAQ^Q209L-derived lines were relatively fragile in 2D culture. At the molecular level, GNAQ^Q209R tumors preferentially engaged the FAK-YAP axis in primary lesions and derived cell lines. Together, these results support an allele-dependent, context-specific trade-off in which higher output GNAQ^Q209L favors rapid in vivo expansion, while GNAQ^Q209R promotes adaptability, potentially via FAK-YAP signaling, nominating allele-stratified therapeutic opportunities.

Mucosal melanoma is a rare and aggressive malignancy arising from anatomically distinct mucosal sites that share a common melanocytic origin but differ in their clinical presentation, biology, and management. Accumulating evidence indicates that the anatomic site of origin fundamentally shapes clinical presentation, immune and microbial microenvironments, molecular drivers, and therapeutic vulnerabilities. In this review, we integrate epidemiologic, clinical, genomic, immunologic, microbiome, and translational data to systematically compare mucosal melanomas arising from the sinonasal tract, oral cavity, anorectal region, and vulvovaginal tract. We highlight striking site-specific differences in patterns of presentation and metastasis, immune and microbiome composition, enrichment of actionable molecular alterations, and responses to therapies. We further discuss how current preclinical models often fail to account for this biologic diversity, limiting translational progress. Collectively, these data support viewing mucosal melanoma as a unified disease entity with clinically meaningful heterogeneity shaped by anatomic site of origin, with important implications for classification, clinical management, and trial design.

Polygenic risk scores can quantify an individual's genetic predisposition by combining the effects of multiple gene variants linked to melanoma susceptibility. Previous studies have demonstrated that PRS is strongly associated with melanoma risk and can improve the identification of high-risk individuals beyond that identified by traditional risk factors. The aim of this study was to calculate PRS for melanoma susceptibility in the Swedish population. Sixty-four single nucleotide polymorphisms, previously associated with melanoma susceptibility, were used to calculate PRS for 599 melanoma patients with or without family history of melanoma and 1180 controls. PRS values were significantly higher among melanoma patients than among controls, with an area under the receiver operating characteristic curve of 0.710. Individuals in the highest PRS decile had a fourfold increased melanoma risk compared with those in the 5th–6th decile. PRS was strongly influenced by the pigmentation-related traits skin phototype and hair color, as well as family history of melanoma and, to some extent, the number of primary melanoma tumors. The results show that PRS is strongly associated with melanoma risk in the Swedish population and may serve as a valuable tool for understanding genetic susceptibility and improving risk stratification in melanoma prevention and clinical management.

Mucosal and acral melanomas are rare subtypes of melanoma with unique clinical and biological features. A dearth of well-established and characterized melanoma cell lines that reflect rare subtypes impedes research on these lethal diseases. We present a protocol developed by exploring various combinations of established techniques that we used to generate mucosal and acral cell lines from patient tissues and patient derived xenografts.