scholarly journals Influence of Interleukin-8 and Neutrophil Extracellular Trap (NET) Formation in the Tumor Microenvironment: Is There a Pathogenic Role?

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Manuela Gonzalez-Aparicio ◽  
Carlos Alfaro
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Tumor Metastasis ◽  
Adoptive Cell Therapy ◽  
Complete Information ◽  
Interleukin 8 ◽  
Neutrophil Extracellular Trap ◽  
Pathogenic Role ◽  
Relevant Role ◽  
The Impact

In this review, we will highlight several studies that revolve around interleukin-8 (IL-8) and show the multiple facets that could take in the tumor microenvironment. Chemokines that attract neutrophils (to a large extent, IL-8) can have a bimodal behavior inducing the migration of them in the first place and later favoring the formation of NETs in the place of emission focus of the chemokine. Also, this mechanism occurs when neutrophils migrate to tumor cells and where the extrusion of NETs in the tumor is observed. A possible participation of NETs in cancer progression was considered; however, until now, it is difficult to decide if NETosis plays a pro- or antitumor role, although it is necessary to emphasize that there is more experimentation focused on the protumorigenic aspect of the NETs. The formation of NETs has a relevant role in the inhibition of the immune response against the tumor generated by neutrophils and in turn favoring the processes involved in the development of tumor metastasis. It is striking that we do not have more complete information about the effects of circulating chemokines on neutrophils in cancer patients and hence the suitability of this review. No one has observed to date the impact that it could have on other cell populations to inhibit the arrival of neutrophils and the formation/elimination of NETs. However, the extent to which NETs affect the function of other cells of the immune system in the tumor context has not been directly demonstrated. It is necessary to identify possible combinations of immunotherapy that involve the modulation of neutrophil activity with other strategies (immunomodulatory antibodies or adoptive cell therapy). Therefore, knowing the mechanisms by which tumors take advantage of this ability of neutrophils to form NETs is very important in the search for antitumor therapies and thus be able to take advantage of the possible immunotherapeutic combinations that we currently have in clinical practice.

scholarly journals The Extracellular Matrix and Vesicles Modulate the Breast Tumor Microenvironment

2020 ◽  
Vol 7 (4) ◽  
pp. 124 ◽  
Author(s):  
Jun Yang ◽  
Gokhan Bahcecioglu ◽  
Pinar Zorlutuna
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Signaling Molecules ◽  
Clinical Applications ◽  
Breast Cancer Progression ◽  
Multiple Roles ◽  
Biophysical Properties ◽  
The Impact

Emerging evidence has shown multiple roles of the tumor microenvironment (TME) components, specifically the extracellular matrix (ECM), in breast cancer development, progression, and metastasis. Aside from the biophysical properties and biochemical composition of the breast ECM, the signaling molecules are extremely important in maintaining homeostasis, and in the breast TME, they serve as the key components that facilitate tumor progression and immune evasion. Extracellular vesicles (EVs), the mediators that convey messages between the cells and their microenvironment through signaling molecules, have just started to capture attention in breast cancer research. In this comprehensive review, we first provide an overview of the impact of ECM in breast cancer progression as well as the alterations occurring in the TME during this process. The critical importance of EVs and their biomolecular contents in breast cancer progression and metastasis are also discussed. Finally, we discuss the potential biomedical or clinical applications of these extracellular components, as well as how they impact treatment outcomes.

scholarly journals Extracellular HSP90 Machineries Build Tumor Microenvironment and Boost Cancer Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Pietro Poggio ◽  
Matteo Sorge ◽  
Laura Seclì ◽  
Mara Brancaccio
Keyword(s):  
Tumor Microenvironment ◽  
Cell Surface ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Diagnostic Tools ◽  
Surface Receptors ◽  
And Behavior ◽  
Cancer Cell Signaling ◽  
The Impact ◽  
Stimulation Of

HSP90 is released by cancer cells in the tumor microenvironment where it associates with different co-chaperones generating complexes with specific functions, ranging from folding and activation of extracellular clients to the stimulation of cell surface receptors. Emerging data indicate that these functions are essential for tumor growth and progression. The understanding of the exact composition of extracellular HSP90 complexes and the molecular mechanisms at the basis of their functions in the tumor microenvironment may represent the first step to design innovative diagnostic tools and new effective therapies. Here we review the impact of extracellular HSP90 complexes on cancer cell signaling and behavior.

scholarly journals Translational control in the tumor microenvironment promotes lung metastasis: Phosphorylation of eIF4E in neutrophils

2018 ◽  
Vol 115 (10) ◽  
pp. E2202-E2209 ◽  
Author(s):  
Nathaniel Robichaud ◽  
Brian E. Hsu ◽  
Roman Istomine ◽  
Fernando Alvarez ◽  
Julianna Blagih ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Translational Control ◽  
Lung Metastases ◽  
Phosphorylation Site ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Metastatic Progression ◽  
The Impact ◽  
In Cells

The translation of mRNAs into proteins serves as a critical regulatory event in gene expression. In the context of cancer, deregulated translation is a hallmark of transformation, promoting the proliferation, survival, and metastatic capabilities of cancer cells. The best-studied factor involved in the translational control of cancer is the eukaryotic translation initiation factor 4E (eIF4E). We and others have shown that eIF4E availability and phosphorylation promote metastasis in mouse models of breast cancer by selectively augmenting the translation of mRNAs involved in invasion and metastasis. However, the impact of translational control in cell types within the tumor microenvironment (TME) is unknown. Here, we demonstrate that regulatory events affecting translation in cells of the TME impact cancer progression. Mice bearing a mutation in the phosphorylation site of eIF4E (S209A) in cells comprising the TME are resistant to the formation of lung metastases in a syngeneic mammary tumor model. This is associated with reduced survival of prometastatic neutrophils due to decreased expression of the antiapoptotic proteins BCL2 and MCL1. Furthermore, we demonstrate that pharmacological inhibition of eIF4E phosphorylation prevents metastatic progression in vivo, supporting the development of phosphorylation inhibitors for clinical use.

scholarly journals Platelets Extracellular Vesicles as Regulators of Cancer Progression—An Updated Perspective

2020 ◽  
Vol 21 (15) ◽  
pp. 5195 ◽  
Author(s):  
Magdalena Żmigrodzka ◽  
Olga Witkowska-Piłaszewicz ◽  
Anna Winnicka
Keyword(s):  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Circulatory System ◽  
Eukaryotic Cells ◽  
Cancer Growth ◽  
Metastasis Formation ◽  
Pathological Conditions ◽  
Membrane Bound ◽  
The Impact

Extracellular vesicles (EVs) are a diverse group of membrane-bound structures secreted in physiological and pathological conditions by prokaryotic and eukaryotic cells. Their role in cell-to-cell communications has been discussed for more than two decades. More attention is paid to assess the impact of EVs in cancer. Numerous papers showed EVs as tumorigenesis regulators, by transferring their cargo molecules (miRNA, DNA, protein, cytokines, receptors, etc.) among cancer cells and cells in the tumor microenvironment. During platelet activation or apoptosis, platelet extracellular vesicles (PEVs) are formed. PEVs present a highly heterogeneous EVs population and are the most abundant EVs group in the circulatory system. The reason for the PEVs heterogeneity are their maternal activators, which is reflected on PEVs size and cargo. As PLTs role in cancer development is well-known, and PEVs are the most numerous EVs in blood, their feasible impact on cancer growth is strongly discussed. PEVs crosstalk could promote proliferation, change tumor microenvironment, favor metastasis formation. In many cases these functions were linked to the transfer into recipient cells specific cargo molecules from PEVs. The article reviews the PEVs biogenesis, cargo molecules, and their impact on the cancer progression.

scholarly journals Arginine and Arginases Modulate Metabolism, Tumor Microenvironment and Prostate Cancer Progression

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4503
Author(s):  
Andreia Matos ◽  
Marcos Carvalho ◽  
Manuel Bicho ◽  
Ricardo Ribeiro
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Urea Cycle ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Prostate Cancer Progression ◽  
Arginine Metabolism ◽  
Arginine Deprivation ◽  
The Impact

Arginine availability and activation of arginine-related pathways at cancer sites have profound effects on the tumor microenvironment, far beyond their well-known role in the hepatic urea cycle. Arginine metabolism impacts not only malignant cells but also the surrounding immune cells behavior, modulating growth, survival, and immunosurveillance mechanisms, either through an arginase-mediated effect on polyamines and proline synthesis, or by the arginine/nitric oxide pathway in tumor cells, antitumor T-cells, myeloid-derived suppressor cells, and macrophages. This review presents evidence concerning the impact of arginine metabolism and arginase activity in the prostate cancer microenvironment, highlighting the recent advances in immunotherapy, which might be relevant for prostate cancer. Even though further research is required, arginine deprivation may represent a novel antimetabolite strategy for the treatment of arginine-dependent prostate cancer.

scholarly journals The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2912 ◽  
Author(s):  
Laurence Blavier ◽  
Ren-Ming Yang ◽  
Yves A. DeClerck
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Inflammatory Cells ◽  
Therapeutic Strategies ◽  
Complex Nature ◽  
Cancer Associated Fibroblasts ◽  
Immunosuppressive Activity ◽  
And Function ◽  
The Impact ◽  
Initial Focus

The contribution of the tumor microenvironment (TME) to cancer progression has been well recognized in recent decades. As cancer therapeutic strategies are increasingly precise and include immunotherapies, knowledge of the nature and function of the TME in a tumor becomes essential. Our understanding of the TME in neuroblastoma (NB), the second most common solid tumor in children, has significantly progressed from an initial focus on its Schwannian component to a better awareness of its complex nature, which includes not only immune but also non-immune cells such as cancer-associated fibroblasts (CAFs), the contribution of which to inflammation and interaction with tumor-associated macrophages (TAMs) is now recognized. Recent studies on the TME landscape of NB tumors also suggest significant differences between MYCN-amplified (MYCN-A) and non-amplified (MYCN-NA) tumors, in their content in stromal and inflammatory cells and their immunosuppressive activity. Extracellular vesicles (EVs) released by cells in the TME and microRNAs (miRs) present in their cargo could play important roles in the communication between NB cells and the TME. This review article discusses these new aspects of the TME in NB and the impact that information on the TME landscape in NB will have in the design of precise, biomarker-integrated clinical trials.

scholarly journals The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

2021 ◽  
Vol 22 (12) ◽  
pp. 6560
Author(s):  
Huogang Wang ◽  
Mingo M. H. Yung ◽  
Hextan Y. S. Ngan ◽  
Karen K. L. Chan ◽  
David W. Chan
Keyword(s):  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Tumor Metastasis ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Macrophage Polarization ◽  
Interleukin 10 ◽  
The Body ◽  
Metastatic Progression ◽  
The Impact

Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to Stephen Paget's “Seed and Soil” hypothesis, metastatic capacity is determined not only by the internal oncogenic driving force but also by the external environment of tumor cells. Throughout the body, macrophages are required for maintaining tissue homeostasis, even in the tumor milieu. To fulfill these multiple functions, macrophages are polarized from the inflammation status (M1-like) to anti-inflammation status (M2-like) to maintain the balance between inflammation and regeneration. However, tumor cell-enforced tumor-associated macrophages (TAMs) (a high M2/M1 ratio status) are associated with poor prognosis for most solid tumors, such as ovarian cancer. In fact, clinical evidence has verified that TAMs, representing up to 50% of the tumor mass, exert both protumor and immunosuppressive effects in promoting tumor metastasis through secretion of interleukin 10 (IL10), transforming growth factor β (TGFβ), and VEGF, expression of PD-1 and consumption of arginine to inhibit T cell anti-tumor function. However, the underlying molecular mechanisms by which the tumor microenvironment favors reprogramming of macrophages to TAMs to establish a premetastatic niche remain controversial. In this review, we examine the latest investigations of TAMs during tumor development, the microenvironmental factors involved in macrophage polarization, and the mechanisms of TAM-mediated tumor metastasis. We hope to dissect the critical roles of TAMs in tumor metastasis, and the potential applications of TAM-targeted therapeutic strategies in cancer treatment are discussed.

Abstract B105: The impact of cholesterol and its metabolites on ovarian tumor microenvironment and cancer progression

2020 ◽  
Author(s):  
Sisi He ◽  
Liqian Ma ◽  
Georgina Cheng ◽  
Betsy Barnick ◽  
Marta Spain ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Ovarian Tumor ◽  
The Impact

scholarly journals Oncoimmunology Meets Organs-on-Chip

2021 ◽  
Vol 8 ◽  
Author(s):  
Fabrizio Mattei ◽  
Sara Andreone ◽  
Arianna Mencattini ◽  
Adele De Ninno ◽  
Luca Businaro ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Ethical Issues ◽  
Early Event ◽  
Long Duration ◽  
Different Types ◽  
On Chip ◽  
The Impact

Oncoimmunology represents a biomedical research discipline coined to study the roles of immune system in cancer progression with the aim of discovering novel strategies to arm it against the malignancy. Infiltration of immune cells within the tumor microenvironment is an early event that results in the establishment of a dynamic cross-talk. Here, immune cells sense antigenic cues to mount a specific anti-tumor response while cancer cells emanate inhibitory signals to dampen it. Animals models have led to giant steps in this research context, and several tools to investigate the effect of immune infiltration in the tumor microenvironment are currently available. However, the use of animals represents a challenge due to ethical issues and long duration of experiments. Organs-on-chip are innovative tools not only to study how cells derived from different organs interact with each other, but also to investigate on the crosstalk between immune cells and different types of cancer cells. In this review, we describe the state-of-the-art of microfluidics and the impact of OOC in the field of oncoimmunology underlining the importance of this system in the advancements on the complexity of tumor microenvironment.

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