Interleukin-8 in Melanoma Pathogenesis, Prognosis and Therapy—An Integrated View into other Neoplasms and Chemokine Networks

Cutaneous melanoma accounts for only about 7% of skin cancers but is causing almost 90% of deaths. Melanoma cells have a distinct repertoire of mutations from other cancers, a high plasticity and degree of mimicry toward vascular phenotype, stemness markers, versatility in evading and suppress host immune control. They exert a significant influence on immune, endothelial and various stromal cells which form tumor microenvironment. The metastatic stage, the leading cause of mortality in this neoplasm, is the outcome of a complex, still poorly understood, cross-talk between tumor and other cell phenotypes. There is accumulating evidence that Interleukin-8 (IL-8) is emblematic for advanced melanomas. This work aimed to present an updated status of IL-8 in melanoma tumor cellular complexity, through a comprehensive analysis including data from other chemokines and neoplasms. The multiple processes and mechanisms surveyed here demonstrate that IL-8 operates following orchestrated programs within signaling webs in melanoma, stromal and vascular cells. Importantly, the yet unknown molecularity regulating IL-8 impact on cells of the immune system could be exploited to overturn tumor fate. The molecular and cellular targets of IL-8 should be brought into the attention of even more intense scientific exploration and valorization in the therapeutical management of melanoma.

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Comparative Expression Analysis of Putative Cancer Stem Cell Markers CD44 and ALDH1A1 in Various Skin Cancer Subtypes

The International Journal of Biological Markers ◽

10.5301/jbm.5000165 ◽

2016 ◽

Vol 31 (1) ◽

pp. 53-61 ◽

Cited By ~ 19

Author(s):

Elham Erfani ◽

Raheleh Roudi ◽

Azadeh Rakhshan ◽

Mehrdad Nasrollahzadeh Sabet ◽

Ahmad Shariftabrizi ◽

...

Keyword(s):

Skin Cancer ◽

Tumor Cells ◽

Clinicopathological Parameters ◽

Stem Cell Markers ◽

Melanoma Tumor ◽

Expression Levels ◽

Cancer Subtypes ◽

Cancer Stem Cell Markers ◽

Skin Cancers ◽

Clinicopathological Significance

Introduction Skin cancers, particularly melanoma, are initiated and maintained by a subpopulation of tumor cells expressing stemness markers that are called cancer stem cells (CSCs). This study aimed to evaluate the expression levels and clinicopathological significance of the putative CSC markers CD44 and ALDH1A1 in patients with skin cancer. Methods The expression levels of CD44 and ALDH1A1 were investigated in 107 skin cancer specimens including 58 (54%) basal cell carcinomas (BCC), 37 (35%) squamous cell carcinomas (SCC), and 12 (11%) melanomas using the tissue microarray (TMA) technique. The correlation of the expression levels of these markers and clinicopathological parameters was then analyzed. Results The expression levels of CD44 and ALDH1A1 were significantly higher in melanoma patients than patients with SCC or BCC (p<0.001 and p = 0.002, respectively). A higher level of CD44 expression was more often found in melanoma tumor cells with a higher rate of recurrence (p = 0.029) and in SCC cases with ulceration (p = 0.01), while there was no significant correlation between ALDH1A1 expression and other clinicopathological parameters. Similarly, coexpression of CD44 and ALDH1A1 (CD44high/ALDH1A1high) was significantly observed in melanoma samples (p<0.001). Conclusions These findings suggest that a CD44high/ALDH1A1high phenotype in melanoma and a CD44high phenotype in SCC can be considered candidates for targeted therapy of skin cancers aiming at CSCs.

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A methodology for carbamate post-translational modification discovery and its application in Escherichia coli

Interface Focus ◽

10.1098/rsfs.2020.0028 ◽

2021 ◽

Vol 11 (2) ◽

pp. 20200028

Author(s):

Victoria L. Linthwaite ◽

Martin J. Cann

Keyword(s):

Escherichia Coli ◽

Carbon Dioxide ◽

Arabidopsis Thaliana ◽

Protein Interactions ◽

Signalling Pathways ◽

Post Translational Modification ◽

Cellular Targets ◽

Biologically Relevant ◽

Cellular Processes ◽

Cell Phenotypes

Carbon dioxide can influence cell phenotypes through the modulation of signalling pathways. CO 2 regulates cellular processes as diverse as metabolism, cellular homeostasis, chemosensing and pathogenesis. This diversity of regulated processes suggests a broadly conserved mechanism for CO 2 interactions with diverse cellular targets. CO 2 is generally unreactive but can interact with neutral amines on protein under normal intracellular conditions to form a carbamate post-translational modification (PTM). We have previously demonstrated the presence of this PTM in a subset of protein produced by the model plant species Arabidopsis thaliana . Here, we describe a detailed methodology for identifying new carbamate PTMs in an extracted soluble proteome under biologically relevant conditions. We apply this methodology to the soluble proteome of the model prokaryote Escherichia coli and identify new carbamate PTMs . The application of this methodology, therefore, supports the hypothesis that the carbamate PTM is both more widespread in biology than previously suspected and may represent a broadly relevant mechanism for CO 2 –protein interactions.

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Leukaemia inhibitory factor and interleukin-8 expression in nonmelanoma skin cancers

Clinical and Experimental Dermatology ◽

10.1046/j.1365-2230.2001.00765.x ◽

2001 ◽

Vol 26 (1) ◽

pp. 72-78 ◽

Cited By ~ 13

Author(s):

Jacek C. Szepietowski ◽

Craig Walker ◽

Dermot B. McKenna ◽

John A. A. Hunter ◽

Roderick C. McKenzie

Keyword(s):

Interleukin 8 ◽

Inhibitory Factor ◽

Leukaemia Inhibitory Factor ◽

Skin Cancers ◽

Nonmelanoma Skin Cancers

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Tumor Blood Vessels and Vasculogenic Mimicry – Current Knowledge and Searching for New Cellular/Molecular Targets of Anti-Angiogenic Therapy

Advances in Cell Biology ◽

10.1515/acb-2017-0005 ◽

2017 ◽

Vol 5 (1) ◽

pp. 50-71 ◽

Cited By ~ 4

Author(s):

Agnieszka Knopik-Skrocka ◽

Patrycja Kręplewska ◽

Donata Jarmołowska-Jurczyszyn

Keyword(s):

Endothelial Cells ◽

Blood Vessels ◽

Tumor Angiogenesis ◽

Current Knowledge ◽

Vasculogenic Mimicry ◽

High Plasticity ◽

Drug Induced ◽

Cellular Targets ◽

Angiogenic Therapy ◽

And Migration

SummaryBlood vessel formation in tumor is defined as tumor angiogenesis. So far, the most known its mechanism is sprouting, which means formation of blood vessels from existing ones, as a result of the proliferation and migration of endothelial cells. The main mitogenic factor of these cells is vascular endothelial growth factor VEGF, acting by VEGFR-2 receptors. Recent studies have provided knowledge about the ability of tumors to form vessel-like structures. The phenomenon was called vascular mimicry. Tumor cells show a high plasticity and they can undergo differentiation to the ones with phenotype similar to endothelial cells. Each of the known tumor angiogenesis mechanisms is a result of many different factors and cell cooperation in tumor microenvironment. Tumor ability to the heterogeneous vascularization forces developing of complex, anti-angiogenic therapy directed to different molecular and cellular targets. Therapies, used so far, often lead to drug-induced hypoxia, which increases tumor cell aggressiveness and metastasis.

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Human Neurofibromas in Co-Culture with Mouse Neurons

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053632 ◽

1982 ◽

Vol 40 ◽

pp. 194-195

Author(s):

R.L. Martuza ◽

T. Liszczak ◽

A. Okun ◽

T-Y Wang

Keyword(s):

Schwann Cell ◽

Schwann Cells ◽

Genetic Disorder ◽

Cranial Nerves ◽

Sympathetic Nerves ◽

Acoustic Neuromas ◽

Spinal Roots ◽

Neural Crest Origin ◽

Multiple Abnormalities ◽

Other Neoplasms

Neurofibromatosis (NF) is an autosomal dominant genetic disorder with a prevalence of 1/3,000 births. The NF mutation causes multiple abnormalities of various cells of neural crest origin. Schwann cell tumors (neurofibromas, acoustic neuromas) are the most common feature of neurofibromatosis although meningiomas, gliomas, and other neoplasms may be seen. The schwann cell tumors commonly develop from the schwann cells associated with sensory or sympathetic nerves or their ganglia. Schwann cell tumors on ventral spinal roots or motor cranial nerves are much less common. Since the sensory neuron membrane is known to contain a mitogenic factor for schwann cells, we have postulated that neurofibromatosis may be due to an abnormal interaction between the nerve and the schwann cell and that this interaction may be hormonally modulated. To test this possibility a system has been developed in which an enriched schwannoma cell culture can be obtained and co-cultured with pure neurons.

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