Dendritic cells are contained within melanocytic nevus nests in vivo and can alter gene expression of epidermal melanocytes in vitro.
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ABSTRACT:
SUBMITTER: Gulati N
PROVIDER: S-EPMC8647048 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We sought to determine what if any changes dendritic cells induce in melanocytes when they are grown together (co-cultured) Comparison of transcriptomes among melanocytes alone, dendritic cells alone, and melanocytes after co-culture with dendritic cells
2014-12-15 | E-GEOD-61353 | biostudies-arrayexpress
Project description:We sought to determine what if any changes dendritic cells induce in melanocytes when they are grown together (co-cultured)
2014-12-15 | GSE61353 | GEO
Project description:BackgroundGiant congenital melanocytic nevi (GCMN) are usually defined as nevi that exceed 20 cm in maximal diameter or 15% of the total body surface area. There have been reports of life-long malignant change risks arising from GCMN, leading to surgical excision of GCMN. This study aims to evaluate the thickness of melanocytes based on clinical factors in order to provide objective information for the complete resection of the lesion.MethodsOverall, 75 patients diagnosed with GCMN between 2000 and 2021 were included, and their clinical records were collected retrospectively. 117 pathologic slides obtained during excision were reviewed to measure nevus thickness. Clinical factors were assessed with a generalized estimated equation model for association with nevus thickness.ResultsThe thickness of nevus was significantly associated with the location and size. Nevus thickness was more superficial in the distal extremity than in the head and trunk (P = 0.003 [head]; P < 0.001 [trunk]; P = 0.091 [Proximal extremity]). Nevi sized 60 cm or more were significantly deeper than those measuring 20-29.9 cm (P = 0.035). An interaction between size and location existed (P < 0.001). Trunk and distal extremity lesions consistently exhibited uniform thickness regardless of lesion size, whereas head and proximal extremity lesions showed variations in thickness based on lesion size.ConclusionGCMNs have differences in thickness according to location and size. Therefore, it is necessary to devise an approach optimized for each patient to treat GCMN. In the study, it was emphasized that the thickness of GCMN is correlated with clinical factors, specifically the location and size of the nevus. Consequently, these findings underscore the need for individualized treatment plans for effective surgical intervention.
| S-EPMC10941407 | biostudies-literature
Project description:BRAF, a cellular oncogene and effector of RAS-mediated signaling, is activated by mutation in approximately 60% of melanomas. Most of these mutations consist of a V600E substitution resulting in constitutive kinase activation. Mutant BRAF thus represents an important therapeutic target in melanoma. In an effort to produce a pre-clinical model of mutant BRAF function in melanoma, we have generated a mouse expressing BRAF V600E targeted to melanocytes. We show that in these transgenic mice, widespread benign melanocytic hyperplasia with histological features of nevi occurs, with biochemical evidence of senescence. Melanocytic hyperplasia progresses to overt melanoma with an incidence dependent on BRAF expression levels. Melanomas show CDKN2A loss, and genetic disruption of the CDKN2A locus greatly enhances melanoma formation, consistent with collaboration between BRAF activation and CDKN2A loss suggested from studies of human melanoma. The development of melanoma also involves activation of the Mapk and Akt signaling pathways and loss of senescence, findings that faithfully recapitulate those seen in human melanomas. This murine model of mutant BRAF-induced melanoma formation thus provides an important tool for identifying further genetic alterations that cooperates with BRAF and that may be useful in enhancing susceptibility to BRAF-targeted therapeutics in melanoma.
| S-EPMC3125533 | biostudies-literature
Project description:UnlabelledDeletion of the entire CDKN2B-CDKN2A gene cluster is among the most common genetic events in cancer. The tumor-promoting effects are generally attributed to loss of CDKN2A-encoded p16 and p14ARF tumor suppressors. The degree to which the associated CDKN2B-encoded p15 loss contributes to human tumorigenesis is unclear. Here, we show that CDKN2B is highly upregulated in benign melanocytic nevi, contributes to maintaining nevus melanocytes in a growth-arrested premalignant state, and is commonly lost in melanoma. Using primary melanocytes isolated directly from freshly excised human nevi naturally expressing the common BRAF(V600E)-activating mutation, nevi progressing to melanoma, and normal melanocytes engineered to inducibly express BRAF(V600E), we show that BRAF activation results in reversible, TGFβ-dependent, p15 induction that halts proliferation. Furthermore, we engineer human skin grafts containing nevus-derived melanocytes to establish a new, architecturally faithful, in vivo melanoma model, and demonstrate that p15 loss promotes the transition from benign nevus to melanoma.SignificanceAlthough BRAF(V600E) mutations cause melanocytes to initially proliferate into benign moles, mechanisms responsible for their eventual growth arrest are unknown. Using melanocytes from human moles, we show that BRAF activation leads to a CDKN2B induction that is critical for restraining BRAF oncogenic effects, and when lost, contributes to melanoma.
| S-EPMC4592422 | biostudies-literature
Project description: Not available
| S-EPMC4165863 | biostudies-literature
Project description:Melanoma and melanocytic nevi harbor shared lineage-specific antigens and oncogenic mutations. Yet, the relationship between the immune system and melanocytic nevi is unclear. Using a patient-derived xenograft (PDX) model, we found that 81.8% of the transplanted nevi underwent spontaneous regression, while peripheral skin remained intact. Nevus-resident CD4+ T helper 1 cells, which exhibited a massive clonal expansion to melanocyte-specific antigens, were responsible for nevus rejection. Boosting regulatory T cell suppressive function with low-dose exogenous human interleukin-2 injection or treatment with a human leukocyte antigen (HLA) class II-blocking antibody prevented nevus rejection. Notably, mice with rejected nevus PDXs were protected from melanoma tumor growth. We detected a parallel CD4+ T cell-dominant immunity in clinically regressing melanocytic nevi. These findings reveal a mechanistic explanation for spontaneous nevus regression in humans and posit the activation of nevus-resident CD4+ effector T cells as a novel strategy for melanoma immunoprevention and treatment.
| S-EPMC8221625 | biostudies-literature
Project description:Background: Cutaneous melanoma has an adjacent nevus remnant upon histological examination in 30% of cases (nevus-associated melanoma, NAM), while it appears de novo for 70% of tumors. Regarding NAM arising in acquired melanocytic nevus, currently there is no evidence on whether NAM more frequently develops in association with a dysplastic or common melanocytic nevus. Objectives: To conduct a systematic review and meta-analysis to investigate the proportion of dysplastic or common melanocytic nevus in NAM associated with acquired nevus. Methods: A systematic literature search is conducted using PubMed, Scopus, and the Cochrane Library. The PRISMA checklist is used. Studies reporting patients diagnosed with NAM arising in an acquired common or dysplastic melanocytic nevus are included. A meta-analysis of proportions is performed using the random-effects model. The magnitude of heterogeneity is assessed with the I2 statistic. Results: A total of 22 studies with 2174 NAMs with an acquired nevus (dysplastic or common) are included. The proportion of dysplastic nevus in NAM varies considerably in the included studies, ranging from 0% to 100%. In the meta-analysis, the overall estimate of the proportion of having a dysplastic nevus in NAM is 51% (95% CI: 39-63%) with high heterogeneity at I2: 95.8% (p < 0.01). A sensitivity meta-analysis of 12 studies that included 30 or more acquired nevus-NAMs (2023 cases) shows that 65% of the NAMs developed in a dysplastic nevus (95% CI: 51-77%). In a meta-analysis of 4 studies reporting invasive-only acquired nevus-NAMs (764 cases), the proportion of dysplastic nevus is 56% (95% CI: 36-75%). Only 2 studies are found reporting in situ NAMs with an acquired nevus, and the pooled estimated proportion of dysplastic nevus is 71% (95% CI: 63-78%). Conclusions: The results of this meta-analysis suggest a higher proportion of dysplastic nevus in acquired nevus-NAM; however, there is considerable uncertainty and high heterogeneity, highlighting the need for future well-designed studies with uniform histopathological definitions for dysplastic nevus remnants which report the type of nevus in NAM separately for invasive melanomas, thin tumors, and by histological subtype.
| S-EPMC9913707 | biostudies-literature
Project description:The nevogenesis of large/giant congenital melanocytic nevus (lgCMN) is a complex biological process including several integral prenatal stages. Limited by ethical concerns, the debate of whether lgCMN develops from the epidermis to the dermis or in the opposite direction remains controversial. With the present study of the accompanying satellite nevi, we tend to support that lgCMN develops from epidermis to dermis. The satellite nevi were divided into 3 groups: big (diameter >10 mm), medium (>5 mm but ≤10 mm), and small (≤5 mm). Hematoxylin and eosin and immunohistochemical staining (SOX10, Ki67, and p16) were performed to compare the nevocyte infiltration depth as well as the positively stained rates among these satellite nevi. Compared to big satellite nevi, less deeply the nevocytes infiltrated the dermis, as well as more cells expressed SOX10 and Ki67 in the epidermis and fewer cells expressed p16 in the dermis of small satellite nevi. Additionally, two specimens were obtained from each of 4 patients who underwent serial resections of lgCMN at an average interval of 1.75 years to examine the histopathological changes. In the present study, satellite nevi of different sizes represent different stages of lgCMN from early to late, deepening our comprehension of the sequential stages of lgCMN nevogenesis. Initially, abnormal nevocytes seeded, proliferated, and spread along the epidermis. At rete ridges that protrude from the papillary dermis within the epidermis, some nevocytes formed nests and gradually penetrated into the dermis. Eventually, the nevocytes infiltrated the dermis and entered a homeostatic state. This study provides new evidence supporting the theory of epidermal-to-dermal nevogenesis in lgCMN.
| S-EPMC9745446 | biostudies-literature
Project description:UnlabelledBackgroundA giant congenital melanocytic nevus (GCMN) is a malformation of the pigment cells. It is a distress to the patients for two reasons: one is disfigurement, and the other is the possibility of malignant changes. However, the underlying mechanisms of the development of GCMN and melanotumorigenesis in GCMN are unknown. Hence, the aim of this study was to identify the proteomic alterations and associated functional pathways in GCMN.ResultsProteomic differences between GCMN (n = 3) and normal skin samples (n = 3) were analyzed by one-dimensional-liquid chromatography-tandem mass spectrometry Relative levels of the selected proteins were validated using western blot analysis. The biological processes associated with the abundance modified proteins were analyzed using bioinformatic tools. Among the 46 abundance modified proteins, expression of 4 proteins was significantly downregulated and expression of 42 proteins was significantly upregulated in GCMN compared to normal skin samples (p < 0.05). More importantly, 31% of the upregulated proteins were implicated in various cancers, with five proteins being specifically related with melanoma. The abundance modified proteins in GCMN were involved in the biological processes of neurotrophin signaling, melanosome, and downregulated of MTA-3 in ER-negative breast tumors. In particular, an increase in the expression of the 14-3-3 protein family members appeared to be associated with key cellular biological functions in GCMN. Western blot analysis confirmed the upregulation of 14-3-3epsilon, 14-3-3 tau, and prohibitin in GCMN.ConclusionThese findings suggest that GCMN exhibits potential proteomic alterations, which may play a role in melanotumorigenesis, and the significant alteration of 14-3-3 family proteins could be a key regulator of the biological pathway remodeling in GCMN.
| S-EPMC3575290 | biostudies-literature