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Melanoma Tissue Structure, Cell Composition, Interactions and Metabolism: From Cancer...
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Melanoma Tissue Structure, Cell Composition, Interactions and Metabolism: From Cancer Pathology to Therapeutic Strategies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 14118

Special Issue Editors

Prof. Dr. Giuseppe Fiume

E-Mail Website
Guest Editor
Department of Experimental and Clinical Medicine, University of Catanzaro “Magna Graecia”, 88100 Catanzaro, Italy
Interests: metabolites profiling of tumor interstitial fluid; immune response; T-lymphocytes; dendritic cells; signal transduction; phagocytosis; antigen presentation; NF-kappaB pathway
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Maria Rosaria Ruocco

E-Mail Website
Guest Editor
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
Interests: effects of non-steroidal anti-inflammatory drugs (NSAIDs) on cancer cells; effects of CDC25 phosphatase inhibitory compounds in tumor cells; preparation and analysis of melanoma cell three-dimensional cultures; paracrine interaction between stromal and tumor cells
Dr. Alessandro Arcucci

E-Mail Website
Guest Editor
Department of Public Health, University of Naples “Federico II”, 80131 Naples, Italy
Interests: preparation and analysis of human primary myofibroblast and breast cancer associated fibroblast three-dimensional cultures; processes regulating myofibroblast inactivation; crosstalk between stromal and cancer cells; toxic effects of molecules targeting melanoma cells

Special Issue Information

Dear Colleagues,

Cutaneous melanoma (CM) represents the most aggressive and drug-resistant type of skin cancer. These features depend on the melanoma cell’s capacity to destroy skin homeostasis and generate a cancer-permissive tumor microenvironment (TME) composed of blood and lymphatic tumor vessels, an extracellular matrix, and noncancerous stromal cells. TME is a safe haven in which melanoma cells survive, escape immune attack, enhance their invasive properties, and acquire a drug-resistant phenotype.

Melanoma cells together with the surrounding TME build a complex dynamic tissue characterized by a remarkable metabolic plasticity influencing therapeutic strategies. In particular, melanoma tissue can change its metabolic choice, structure, composition, mechanical, and cellular properties to accommodate the needs of melanoma cells during cancer evolution.

In this Special Issue, we welcome authors to submit original research and review articles contributing to better understanding topics that can include but are not limited to:

  • Role of melanoma cells in the establishment and remodeling of TME;
  • Metabolism of melanoma cells and noncancerous stromal cells;
  • Role of melanoma cells and TME in cancer;
  • Role of melanoma cells and TME interactions in the regulation of CM development, progression, immune escape, and therapy resistance;
  • Therapeutic strategies targeting melanoma tissue.

Prof. Dr. Giuseppe Fiume
Prof. Dr. Maria Rosaria Ruocco
Dr. Alessandro Arcucci
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cutaneous melanoma
  • tumor microenvironment
  • melanoma cells
  • stromal cells
  • metabolism
  • therapeutic strategies
  • immune escape
  • therapy resistance

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Published Papers (4 papers)

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Research

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13 pages, 2512 KiB  
Article
Development of Sesamol Carbamate-L-Phenylalanine Prodrug Targeting L-Type Amino Acid Transporter1 (LAT1) as a Potential Antiproliferative Agent against Melanoma
by Tarapong Srisongkram, Katayun Bahrami, Juulia Järvinen, Juri Timonen, Jarkko Rautio and Natthida Weerapreeyakul
Int. J. Mol. Sci. 2022, 23(15), 8446; https://doi.org/10.3390/ijms23158446 - 30 Jul 2022
Cited by 7 | Viewed by 2520
Abstract
Sesamol is a compound reported to have anti-melanogenesis and anti-melanoma actions. Sesamol, however, has low intracellular drug concentration and fast excretion, which can limit its benefits in the clinic. To overcome this drawback and increase intracellular delivery of sesamol into the target melanoma, [...] Read more.
Sesamol is a compound reported to have anti-melanogenesis and anti-melanoma actions. Sesamol, however, has low intracellular drug concentration and fast excretion, which can limit its benefits in the clinic. To overcome this drawback and increase intracellular delivery of sesamol into the target melanoma, research has focused on L-type amino acid transporter 1 (LAT1)-mediated prodrug delivery into melanoma cells. The sesamol prodrug was designed by conjugating sesamol with L-phenylalanine at the para position with a carbamate bond. LAT1 targeting was evaluated vis-à-vis a competitive [14C]-leucine uptake inhibition. The sesamol prodrug has a higher [14C]-leucine uptake inhibition than sesamol in human LAT1-transfected HEK293 cells. Moreover, the sesamol prodrug was taken up by LAT1-mediated transport into SK-MEL-2 cells more effectively than sesamol. The sesamol prodrug underwent complete hydrolysis, releasing the active sesamol at 72 h, which significantly exerted its cytotoxicity (IC50 of 29.3 µM) against SK-MEL-cells more than sesamol alone. Taken together, the strategy for LAT1-mediated prodrug delivery has utility for the selective uptake of sesamol, thereby increasing its intracellular concentration and antiproliferation activity, targeting melanoma SK-MEL-2 cells that overexpress the LAT1 protein. The sesamol prodrug thus warrants further evaluation in an in vivo model. Full article
(This article belongs to the Special Issue Melanoma Tissue Structure, Cell Composition, Interactions and Metabolism: From Cancer Pathology to Therapeutic Strategies)
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20 pages, 3253 KiB  
Article
HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma
by Markus V. Heppt, Anja Wessely, Eva Hornig, Claudia Kammerbauer, Saskia A. Graf, Robert Besch, Lars E. French, Alexander Matthies, Silke Kuphal, Melanie Kappelmann-Fenzl, Anja K. Bosserhoff and Carola Berking
Int. J. Mol. Sci. 2022, 23(2), 849; https://doi.org/10.3390/ijms23020849 - 13 Jan 2022
Cited by 6 | Viewed by 2841
Abstract
The neural crest transcription factor BRN3A is essential for the proliferation and survival of melanoma cells. It is frequently expressed in melanoma but not in normal melanocytes or benign nevi. The mechanisms underlying the aberrant expression of BRN3A are unknown. Here, we investigated [...] Read more.
The neural crest transcription factor BRN3A is essential for the proliferation and survival of melanoma cells. It is frequently expressed in melanoma but not in normal melanocytes or benign nevi. The mechanisms underlying the aberrant expression of BRN3A are unknown. Here, we investigated the epigenetic regulation of BRN3A in melanocytes and melanoma cell lines treated with DNA methyltransferase (DNMT), histone acetyltransferase (HAT), and histone deacetylase (HDAC) inhibitors. DNMT and HAT inhibition did not significantly alter BRN3A expression levels, whereas panHDAC inhibition by trichostatin A led to increased expression. Treatment with the isoform-specific HDAC inhibitor mocetinostat, but not with PCI-34051, also increased BRN3A expression levels, suggesting that class I HDACs HDAC1, HDAC2, and HDAC3, and class IV HDAC11, were involved in the regulation of BRN3A expression. Transient silencing of HDACs 1, 2, 3, and 11 by siRNAs revealed that, specifically, HDAC2 inhibition was able to increase BRN3A expression. ChIP-Seq analysis uncovered that HDAC2 inhibition specifically increased H3K27ac levels at a distal enhancer region of the BRN3A gene. Altogether, our data suggest that HDAC2 is a key epigenetic regulator of BRN3A in melanocytes and melanoma cells. These results highlight the importance of epigenetic mechanisms in regulating melanoma oncogenes. Full article
(This article belongs to the Special Issue Melanoma Tissue Structure, Cell Composition, Interactions and Metabolism: From Cancer Pathology to Therapeutic Strategies)
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Review

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17 pages, 323 KiB  
Review
The Treatment of Advanced Melanoma: Therapeutic Update
by Alessia Villani, Luca Potestio, Gabriella Fabbrocini, Giancarlo Troncone, Umberto Malapelle and Massimiliano Scalvenzi
Int. J. Mol. Sci. 2022, 23(12), 6388; https://doi.org/10.3390/ijms23126388 - 7 Jun 2022
Cited by 53 | Viewed by 4000
Abstract
Cutaneous melanoma is the main cause of death for skin cancer. The majority of patients with a diagnosis of melanoma have localized disease, which can be successfully treated with surgical treatment. However, the surgical approach is not curative for advanced melanoma (AM). Indeed, [...] Read more.
Cutaneous melanoma is the main cause of death for skin cancer. The majority of patients with a diagnosis of melanoma have localized disease, which can be successfully treated with surgical treatment. However, the surgical approach is not curative for advanced melanoma (AM). Indeed, the management of AM is still challenging, since melanoma is the solid tumor with the highest number of mutations and cancer cells have the capacity to evade the immune system. In the past, the treatment of AM relied on chemotherapeutic agents, without showing efficacy data. Recent knowledge on melanoma pathogenesis as well as the introduction of immunotherapies, targeted therapies vaccines, small molecules, and combination therapies has revolutionized AM management, showing promising results in terms of effectiveness and safety. The aim of this review is to assess and to discuss the role of emerging therapies for AM management in order to obtain a complete overview of the currently available treatment options and future perspectives. Full article
(This article belongs to the Special Issue Melanoma Tissue Structure, Cell Composition, Interactions and Metabolism: From Cancer Pathology to Therapeutic Strategies)
16 pages, 558 KiB  
Review
Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma
by Hikaru Nanamori and Yu Sawada
Int. J. Mol. Sci. 2022, 23(3), 1119; https://doi.org/10.3390/ijms23031119 - 20 Jan 2022
Cited by 13 | Viewed by 3586
Abstract
Malignant melanoma is one of the representative skin cancers with unfavorable clinical behavior. Immunotherapy is currently used for the treatment, and it dramatically improves clinical outcomes in patients with advanced malignant melanoma. On the other hand, not all these patients can obtain therapeutic [...] Read more.
Malignant melanoma is one of the representative skin cancers with unfavorable clinical behavior. Immunotherapy is currently used for the treatment, and it dramatically improves clinical outcomes in patients with advanced malignant melanoma. On the other hand, not all these patients can obtain therapeutic efficacy. To overcome this limitation of current immunotherapy, epigenetic modification is a highlighted issue for clinicians. Epigenetic modification is involved in various physiological and pathological conditions in the skin. Recent studies identified that skin cancer, especially malignant melanoma, has advantages in tumor development, indicating that epigenetic manipulation for regulation of gene expression in the tumor can be expected to result in additional therapeutic efficacy during immunotherapy. In this review, we focus on the detailed molecular mechanism of epigenetic modification in immunotherapy, especially anti-PD-1/PD-L1 antibody treatment for malignant melanoma. Full article
(This article belongs to the Special Issue Melanoma Tissue Structure, Cell Composition, Interactions and Metabolism: From Cancer Pathology to Therapeutic Strategies)
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