scholarly journals Role of miRNAs in Melanoma Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 326 ◽  
Author(s):  
Anna Gajos-Michniewicz ◽  
Malgorzata Czyz
Keyword(s):  
Target Genes ◽  
Selective Advantage ◽  
Tumour Microenvironment ◽  
Response To Treatment ◽  
Melanoma Metastasis ◽  
Liquid Biopsies ◽  
Tumour Metastasis ◽  
Multistep Process ◽  
Ecm Extracellular Matrix

Tumour metastasis is a multistep process. Melanoma is a highly aggressive cancer and metastasis accounts for the majority of patient deaths. microRNAs (miRNAs) are non-coding RNAs that affect the expression of their target genes. When aberrantly expressed they contribute to the development of melanoma. While miRNAs can act locally in the cell where they are synthesized, they can also influence the phenotype of neighboring melanoma cells or execute their function in the direct tumour microenvironment by modulating ECM (extracellular matrix) and the activity of fibroblasts, endothelial cells, and immune cells. miRNAs are involved in all stages of melanoma metastasis, including intravasation into the lumina of vessels, survival during circulation in cardiovascular or lymphatic systems, extravasation, and formation of the pre-metastatic niche in distant organs. miRNAs contribute to metabolic alterations that provide a selective advantage during melanoma progression. They play an important role in the development of drug resistance, including resistance to targeted therapies and immunotherapies. Distinct profiles of miRNA expression are detected at each step of melanoma development. Since miRNAs can be detected in liquid biopsies, they are considered biomarkers of early disease stages or response to treatment. This review summarizes recent findings regarding the role of miRNAs in melanoma metastasis.

scholarly journals New Insights into Molecular Oncogenesis and Therapy of Uveal Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 694 ◽  
Author(s):  
Sara Silvia Violanti ◽  
Ilaria Bononi ◽  
Carla Enrica Gallenga ◽  
Fernanda Martini ◽  
Mauro Tognon ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Target Genes ◽  
Therapeutic Strategies ◽  
Biomedical Sciences ◽  
Therapeutic Approaches ◽  
Common Cancer ◽  
Multistep Process ◽  
Systemic Adjuvant Therapy ◽  
Novel Therapeutic

Uveal melanoma (UM), which is the most common cancer of the eye, was investigated in recent years by many teams in the field of biomedical sciences and eye clinicians. New knowledge was acquired on molecular pathways found to be dysregulated during the multistep process of oncogenesis, whereas novel therapeutic approaches gave significant results in the clinical applications. Uveal melanoma-affected patients greatly benefited from recent advances of the research in this eye cancer. Tumour biology, genetics, epigenetics and immunology contributed significantly in elucidating the role of different genes and related pathways during uveal melanoma onset/progression and UM treatments. Indeed, these investigations allowed identification of new target genes and to develop new therapeutic strategies/compounds to cure this aggressive melanoma of the eye. Unfortunately, the advances reported in the treatment of cutaneous melanoma have not produced analogous benefits in metastatic uveal melanoma. Nowadays, no systemic adjuvant therapy has been shown to improve overall survival or reduce the risk of metastasis. However, the increasing knowledge of this disease, and the encouraging results seen in clinical trials, offer promise for future effective therapies. Herein, different pathways/genes involved in uveal melanoma onset/progression were taken into consideration, together with novel therapeutic approaches.

scholarly journals Acidic and Hypoxic Microenvironment in Melanoma: Impact of Tumour Exosomes on Disease Progression

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3311
Author(s):  
Zaira Boussadia ◽  
Adriana Rosa Gambardella ◽  
Fabrizio Mattei ◽  
Isabella Parolini
Keyword(s):  
Malignant Melanoma ◽  
Immune Cells ◽  
Stromal Cells ◽  
Immune Surveillance ◽  
Tumour Microenvironment ◽  
Response To Treatment ◽  
Malignant Phenotype ◽  
Hypoxic Conditions ◽  
Melanoma Diagnosis

The mechanisms of melanoma progression have been extensively studied in the last decade, and despite the diagnostic and therapeutic advancements pursued, malignant melanoma still accounts for 60% of skin cancer deaths. Therefore, research efforts are required to better define the intercellular molecular steps underlying the melanoma development. In an attempt to represent the complexity of the tumour microenvironment (TME), here we analysed the studies on melanoma in acidic and hypoxic microenvironments and the interactions with stromal and immune cells. Within TME, acidity and hypoxia force melanoma cells to adapt and to evolve into a malignant phenotype, through the cooperation of the tumour-surrounding stromal cells and the escape from the immune surveillance. The role of tumour exosomes in the intercellular crosstalk has been generally addressed, but less studied in acidic and hypoxic conditions. Thus, this review aims to summarize the role of acidic and hypoxic microenvironment in melanoma biology, as well as the role played by melanoma-derived exosomes (Mexo) under these conditions. We also present a perspective on the characteristics of acidic and hypoxic exosomes to disclose molecules, to be further considered as promising biomarkers for an early detection of the disease. An update on the use of exosomes in melanoma diagnosis, prognosis and response to treatment will be also provided and discussed.

scholarly journals IL-6 Activities in the Tumour Microenvironment. Part 1

2019 ◽  
Vol 7 (14) ◽  
pp. 2391-2398 ◽  
Author(s):  
Dimitur Chavdarov Chonov ◽  
Maria Magdalena Krasimirova Ignatova ◽  
Julian Rumenov Ananiev ◽  
Maya Vladova Gulubova
Keyword(s):  
Target Genes ◽  
Elevated Serum ◽  
Serum Levels ◽  
Tumour Microenvironment ◽  
High Endothelial Venules ◽  
Tumour Immunity ◽  
Membrane Bound ◽  
In Trans ◽  
Transcription 3

The predominant role of IL-6 in cancer is its key promotion of tumour growth. IL-6 binds IL-6 receptor (IL-6R) and the membrane-bound glycoprotein gp130. The complex I-6/IL-6R/gp130 starts the Janus kinases (JAKs) and signal transducer and activator of transcription 3 (STAT3) or JAK/STAT3 pathway. IL-6R exits in two forms: a membrane-bound IL-6Rα subunit (mIL-6R) that participates in classic signalling pathway and soluble IL-6R subunit (sIL-6R) engaged in trans-signalling. The pro-tumour functions of IL-6 are associated with STAT3, a major oncogenic transcription factor that triggers up-regulation of target genes responsible for tumour cell survival. IL-6 combined with TGF-β induces proliferation of pathogenic Th17 cells. The anti-tumour function of IL-6 is the promotion of anti-tumour immunity. IL-6 trans-signaling contributed to transmigration of lymphocytes in high endothelial venules (HEV). Dendritic cell (DC) secreted IL-6 in the lymph node influences the activation, distribution and polarisation of the immune response. Elevated serum levels of IL-6 and increased expression of IL-6 in tumour tissue are negative prognostic marker for patients’ survival.

scholarly journals MicroRNAs and miRceptors: a new mechanism of action for intercellular communication

2017 ◽  
Vol 373 (1737) ◽  
pp. 20160486 ◽  
Author(s):  
Muller Fabbri
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Mechanism Of Action ◽  
Intercellular Communication ◽  
Target Genes ◽  
Tumour Microenvironment ◽  
Signalling Pathways ◽  
Non Coding Rnas ◽  
Cancerous Cells

MicroRNAs (miRs) are small non-coding RNAs (ncRNAs) that control the expression of target genes by modulating (usually inhibiting) their translation into proteins. This ‘traditional’ mechanism of action of miRs has been recently challenged by new discoveries pointing towards a role of miRs as ‘hormones’, capable of binding to proteic receptors (miRceptors) and triggering their downstream signalling pathways. These findings harbour particular significance within the tumour microenvironment (TME), defined as the variety of non-cancerous cells surrounding cancer cells, but are relevant also for other diseases. In recent years it has become clearer that the TME does not passively assist the growth of cancer cells but contributes to its biology. Some of the mediators of the intercellular communication between cancer cells and TME are miRs shuttled within exosomes, a subtype of cellular released extracellular vesicles. This article will highlight the most recent findings on the biological implications of miR–miRceptor interactions for the biology of the TME and other diseases, and will provide some perspectives on the future development of this fascinating research. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

scholarly journals Tumour–adipose tissue crosstalk: fuelling tumour metastasis by extracellular vesicles

2017 ◽  
Vol 373 (1737) ◽  
pp. 20160485 ◽  
Author(s):  
Lucía Robado de Lope ◽  
Olwen Leaman Alcíbar ◽  
Ana Amor López ◽  
Marta Hergueta-Redondo ◽  
Héctor Peinado
Keyword(s):  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Breast And Ovarian Cancer ◽  
Tumour Metastasis ◽  
Bone Marrow Derived Cells

During metastasis, tumour cells must communicate with their microenvironment by secreted soluble factors and extracellular vesicles. Different stromal cell types (e.g. bone marrow–derived cells, endothelial cells and fibroblasts) influence the growth and progression of tumours. In recent years, interest has extended to other cell types in the tumour microenvironment such as adipocytes and adipose tissue–derived mesenchymal stem cells. Indeed, obesity is becoming pandemic in some developing countries and it is now considered to be a risk factor for cancer progression. However, the true impact of obesity on the metastatic behaviour of tumours is still not yet fully understood. In this ‘Perspective’ article, we will discuss the potential influence of obesity on tumour metastasis, mainly in melanoma, breast and ovarian cancer. We summarize the main mechanisms involved with special attention to the role of extracellular vesicles in this process. We envisage that besides having a direct impact on tumour cells, obesity systemically preconditions the tumour microenvironment for future metastasis by favouring the formation of pro-inflammatory niches. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

scholarly journals miRNAs in the Regulation of Cancer Immune Response: Effect of miRNAs on Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6145
Author(s):  
Faheem Hyder Pottoo ◽  
Ashif Iqubal ◽  
Mohammad Kashif Iqubal ◽  
Mohammed Salahuddin ◽  
Jawad Ur Rahman ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Target Genes ◽  
Immune Escape ◽  
Clinical Success ◽  
Therapeutic Option ◽  
Tumour Microenvironment ◽  
Signalling Pathways ◽  
Different Types ◽  
Immune Checkpoint Blockers

In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system’s multiple signalling pathways by binding to the 3′-UTR of target genes. miRNAs possess a unique advantage in modulating multiple targets of either the same or different signalling pathways. Therefore, miRNA follows a ‘one drug multiple target’ hypothesis. Attempts are made to explore the therapeutic promise of miRNAs in cancer so that it can be transported from bench to bedside for successful immunotherapeutic results. Therefore, in the current manuscript, we discussed, in detail, the mechanism and role of miRNAs in different types of cancers relating to the immune system, its diagnostic and therapeutic aspect, the effect on immune escape, immune-checkpoint molecules, and the tumour microenvironment. We have also discussed the existing limitations, clinical success and the prospective use of miRNAs in cancer.

The role of DUBs in the post-translational control of cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz
Keyword(s):  
Cell Migration ◽  
Translational Control ◽  
Epithelial To Mesenchymal Transition ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Tgfβ Receptors ◽  
Fundamental Process ◽  
Multistep Process

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.

Juvenile xanthogranuloma of the subdural spaces mimicking chronic hematoma with positive FDG uptake on PET: case report

2020 ◽  
Vol 26 (4) ◽  
pp. 449-453
Author(s):  
Jacob A. Kahn ◽  
Jeffrey T. Waltz ◽  
Ramin M. Eskandari ◽  
Cynthia T. Welsh ◽  
Michael U. Antonucci
Keyword(s):  
Potential Role ◽  
Response To Treatment ◽  
Juvenile Xanthogranuloma ◽  
Imaging Features ◽  
Limited Information ◽  
Advanced Imaging ◽  
Systemic Involvement ◽  
The Central Nervous System ◽  
Infancy And Early Childhood

The authors report an unusual presentation of juvenile xanthogranuloma (JXG), a non–Langerhans cell histiocytosis of infancy and early childhood. This entity typically presents as a cutaneous head or neck nodule but can manifest with more systemic involvement including in the central nervous system. However, currently there is limited information regarding specific imaging features differentiating JXG from other neuropathological entities, with diagnosis typically made only after tissue sampling. The authors reviewed the initial images of a young patient with shunt-treated hydrocephalus and enlarging, chronic, extraaxial processes presumed to reflect subdural collections from overshunting, and they examine the operative discovery of a mass lesion that was pathologically proven to be JXG. Their results incorporate the important associated histological and advanced imaging features, including previously unreported metabolic activity on FDG PET. Ultimately, the case underscores the need to consider JXG in differential diagnoses of pediatric intracranial masses and highlights the potential role of PET in the initial diagnosis and response to treatment.

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