scholarly journals Emerging Role of Extracellular Vesicles and Cellular Communication in Metastasis

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3429
Author(s):  
Aisling Forder ◽  
Chi-Yun Hsing ◽  
Jessica Trejo Vazquez ◽  
Cathie Garnis
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Metastatic Niche ◽  
Novel Treatment ◽  
Membrane Bound ◽  
Novel Treatment Strategies

Communication between cancer cells and the surrounding stromal cells of the tumor microenvironment (TME) plays a key role in promoting metastasis, which is the major cause of cancer death. Small membrane-bound particles called extracellular vesicles (EVs) are released from both cancer and stromal cells and have a key role in mediating this communication through transport of cargo such as various RNA species (mRNA, miRNA, lncRNA), proteins, and lipids. Tumor-secreted EVs have been observed to induce a pro-tumorigenic phenotype in non-malignant cells of the stroma, including fibroblasts, endothelial cells, and local immune cells. These cancer-associated cells then drive metastasis by mechanisms such as increasing the invasiveness of cancer cells, facilitating angiogenesis, and promoting the formation of the pre-metastatic niche. This review will cover the role of EV-mediated signaling in the TME during metastasis and highlight the therapeutic potential of targeting these pathways to develop biomarkers and novel treatment strategies.

scholarly journals Role of subnetworks mediated by $$\hbox {TNF}\alpha$$, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rakesh Pandey ◽  
Yusur Al-Nuaimi ◽  
Rajiv Kumar Mishra ◽  
Sarah K. Spurgeon ◽  
Marc Goodfellow
Keyword(s):  
Complex Network ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Tnf Alpha ◽  
Cell Network ◽  
Novel Treatment ◽  
Future Drug ◽  
Novel Treatment Strategies

AbstractPsoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving $$\hbox {TNF}_{\alpha }$$ TNF α , IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of $$\hbox {TNF}_{\alpha }$$ TNF α , IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of $$\hbox {TNF}_{\alpha }$$ TNF α would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis.

scholarly journals Extracellular vesicles and immunogenic stress in cancer

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Qi Wu ◽  
Hanpu Zhang ◽  
Si Sun ◽  
Lijun Wang ◽  
Shengrong Sun
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Stress Responses ◽  
Stromal Cells ◽  
Immune Status ◽  
Immune Surveillance ◽  
Cell Communication ◽  
Treatment Strategies ◽  
Stress Reactions ◽  
Damage Response

AbstractTumor progression requires bidirectional cell-to-cell communication within a complex tumor microenvironment (TME). Extracellular vesicles (EVs) as carriers have the capacity to shuttle regulatory molecules, including nucleic acids, proteins, and lipids, between cancer cells and multiple stromal cells, inducing remarkable phenotypic alterations in the TME. Recently proposed the concept “immunogenic stress”, which means in some stressed microenvironment, cancer cells can release EVs containing specific immunoregulatory mediators, depending on the initiating stress-associated pathway, thereby provoking the changes of immune status in the TME. Considerable evidence has revealed that the intracellular mechanisms underlying the response to diverse stresses are mainly autophagy, endoplasmic reticulum (ER) stress reactions and the DNA damage response (DDR). In addition, the activation of immunogenic stress responses endows hosts with immune surveillance capacity; in contrast, several cargoes in EVs under immunogenic stress trigger a passive immune response by mediating the function of immune cells. This review discusses the current understanding of the immunogenic stress pathways in cancer and describes the interrelation between EVs and immunogenic stress to propose potential treatment strategies and biomarkers.

scholarly journals Provasopressin expression by breast cancer cells: implications for growth and novel treatment strategies

2005 ◽  
Vol 95 (3) ◽  
pp. 265-277 ◽  
Author(s):  
Brendan P. Keegan ◽  
Bonnie L. Akerman ◽  
Christel Péqueux ◽  
William G. North
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Treatment Strategies ◽  
Novel Treatment ◽  
Novel Treatment Strategies

scholarly journals The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

2020 ◽  
Vol 21 (18) ◽  
pp. 6837 ◽  
Author(s):  
Issraa Shoucair ◽  
Fernanda Weber Mello ◽  
James Jabalee ◽  
Saeideh Maleki ◽  
Cathie Garnis
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapy Resistance ◽  
The Other ◽  
Cancer Associated Fibroblasts ◽  
Metastatic Niche ◽  
Niche Formation ◽  
Molecular Aspects

Extracellular vesicles (EVs) play a key role in the communication between cancer cells and stromal components of the tumor microenvironment (TME). In this context, cancer cell-derived EVs can regulate the activation of a CAF phenotype in TME cells, which can be mediated by several EV cargos (e.g., miRNA, proteins, mRNA and lncRNAs). On the other hand, CAF-derived EVs can mediate several processes during tumorigenesis, including tumor growth, invasion, metastasis, and therapy resistance. This review aimed to discuss the molecular aspects of EV-based cross-talk between CAFs and cancer cells during tumorigenesis, in addition to assessing the roles of EV cargo in therapy resistance and pre-metastatic niche formation.

scholarly journals A Breath of Fresh Air in the Fog of Antimicrobial Resistance: Inhaled Polymyxins for Gram-Negative Pneumonia

Antibiotics ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 27 ◽  
Author(s):  
Mark Biagi ◽  
David Butler ◽  
Xing Tan ◽  
Samah Qasmieh ◽  
Eric Wenzler
Keyword(s):  
Potential Role ◽  
Treatment Strategies ◽  
Comprehensive Overview ◽  
Gram Negative ◽  
Novel Treatment ◽  
Pharmacodynamic Profile ◽  
Inhaled Antibiotics ◽  
Novel Treatment Strategies ◽  
Significant Attention

Despite advancements in therapy, pneumonia remains the leading cause of death due to infectious diseases. Novel treatment strategies are desperately needed to optimize the antimicrobial therapy of patients suffering from this disease. One such strategy that has recently garnered significant attention is the use of inhaled antibiotics to rapidly achieve therapeutic concentrations directly at the site of infection. In particular, there is significant interest in the role of inhaled polymyxins for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, due to their retained activity against multi-drug resistant Gram-negative pathogens, including Acinetobacter baumannii and Pseudomonas aeruginosa. This review will provide a comprehensive overview of the pharmacokinetic/pharmacodynamic profile, clinical outcomes, safety, and potential role of inhaled polymyxins in clinical practice.

scholarly journals Metabolic signaling functions of ER–mitochondria contact sites: role in metabolic diseases

2017 ◽  
Vol 58 (2) ◽  
pp. R87-R106 ◽  
Author(s):  
Emily Tubbs ◽  
Jennifer Rieusset
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Treatment Strategies ◽  
Contact Sites ◽  
Novel Treatment ◽  
Functional Features ◽  
Novel Treatment Strategies

Beyond the maintenance of cellular homeostasis and the determination of cell fate, ER–mitochondria contact sites, defined as mitochondria-associated membranes (MAM), start to emerge as an important signaling hub that integrates nutrient and hormonal stimuli and adapts cellular metabolism. Here, we summarize the established structural and functional features of MAM and mainly focus on the latest breakthroughs highlighting a crucial role of organelle crosstalk in the control of metabolic homeostasis. Lastly, we discuss recent studies that have revealed the importance of MAM in not only metabolic diseases but also in other pathologies with disrupted metabolism, shedding light on potential common molecular mechanisms and leading hopefully to novel treatment strategies.

scholarly journals Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications

2020 ◽  
Vol 9 (6) ◽  
pp. 1905 ◽  
Author(s):  
Christopher J. Hill ◽  
Marwa Fakhreldin ◽  
Alison Maclean ◽  
Lucy Dobson ◽  
Lewis Nancarrow ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Chronic Condition ◽  
Treatment Strategies ◽  
Clinical Implications ◽  
Fallopian Tubes ◽  
Anatomical Distribution ◽  
Epithelial Cancers ◽  
Novel Treatment ◽  
Clinical Consequences ◽  
Novel Treatment Strategies

Endometriosis is a common, oestrogen driven chronic condition, where endometrium-like epithelial and stromal cells exist in ectopic sites. At present, no curative treatments are available and the existing evidence for disease progression is conflicting. The pathogenesis is still unknown and evidently complex, as mechanisms of initiation may depend on the anatomical distribution of endometriotic lesions. However, amongst the numerous theories and plethora of mechanisms, contributions of the fallopian tubes (FT) to endometriosis are rarely discussed. The FT are implicated in all endometriosis associated symptomatology and clinical consequences; they may contribute to the origin of endometriotic tissue, determine the sites for ectopic lesion establishment and act as conduits for the spread of proinflammatory media. Here, we examine the available evidence for the contribution of the human FT to the origin, pathogenesis and symptoms/clinical consequences of endometriosis. We also examine the broader topic linking endometriosis and the FT epithelium to the genesis of ovarian epithelial cancers. Further studies elucidating the distinct functional and phenotypical characteristics of FT mucosa may allow the development of novel treatment strategies for endometriosis that are potentially curative.

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