scholarly journals Inflammatory Cytokine Signaling during Development of Pancreatic and Prostate Cancers

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Geou-Yarh Liou
Keyword(s):  
Endothelial Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Inflammatory Cytokine ◽  
Cancer Development ◽  
Cytokine Signaling ◽  
Environment Effects ◽  
Tumor Environment ◽  
Prostate Cancers ◽  
Different Sources

Inflammation is essential for many diseases including cancer. Activation and recruitment of immune cells during inflammation result in a cytokine- and chemokine-enriched cell environment, which affects cancer development. Since each type of cancer has its unique tumor environment, effects of cytokines from different sources such as tumor-infiltrating immune cells, stromal cells, endothelial cells, and cancer cells on cancer development can be quite complex. In this review, how immune cells contribute to tumorigenesis of pancreatic and prostate cancers through their secreted cytokines is discussed. In addition, the cytokine signaling that tumor cells of pancreatic and prostate cancers utilize to benefit their own survival is delineated.

scholarly journals The Emerging Roles of Pericytes in Modulating Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Ruipu Sun ◽  
Xiangzhan Kong ◽  
Xiaoyi Qiu ◽  
Cheng Huang ◽  
Ping-Pui Wong
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Stromal Cells ◽  
Direct Interaction ◽  
Cancer Growth ◽  
Mural Cells ◽  
Current Review ◽  
Recent Advancement

Pericytes (PCs), known as mural cells, play an important blood vessel (BV) supporting role in regulating vascular stabilization, permeability and blood flow in microcirculation as well as blood brain barrier. In carcinogenesis, defective interaction between PCs and endothelial cells (ECs) contributes to the formation of leaky, chaotic and dysfunctional vasculature in tumors. However, recent works from other laboratories and our own demonstrate that the direct interaction between PCs and other stromal cells/cancer cells can modulate tumor microenvironment (TME) to favor cancer growth and progression, independent of its BV supporting role. Furthermore, accumulating evidence suggests that PCs have an immunomodulatory role. In the current review, we focus on recent advancement in understanding PC’s regulatory role in the TME by communicating with ECs, immune cells, and tumor cells, and discuss how we can target PC’s functions to re-model TME for an improved cancer treatment strategy.

scholarly journals Active roles of dysfunctional vascular endothelium in fibrosis and cancer

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Tien Hsu ◽  
Hieu-Huy Nguyen-Tran ◽  
Maria Trojanowska
Keyword(s):  
Endothelial Cells ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Vascular Endothelium ◽  
Pathological Condition ◽  
Cytokine Signaling ◽  
Mesenchymal Transition ◽  
Tissue Inflammation ◽  
Endothelial To Mesenchymal Transition ◽  
Pathogenic Process

Abstract Chronic inflammation is the underlying pathological condition that results in fibrotic diseases. More recently, many forms of cancer have also been linked to chronic tissue inflammation. While stromal immune cells and myofibroblasts have been recognized as major contributors of cytokines and growth factors that foster the formation of fibrotic tissue, the endothelium has traditionally been regarded as a passive player in the pathogenic process, or even as a barrier since it provides a physical divide between the circulating immune cells and the inflamed tissues. Recent findings, however, have indicated that endothelial cells in fact play a crucial role in the inflammatory response. Endothelial cells can be activated by cytokine signaling and express inflammatory markers, which can sustain or exacerbate the inflammatory process. For example, the activated endothelium can recruit and activate leukocytes, thus perpetuating tissue inflammation, while sustained stimulation of endothelial cells may lead to endothelial-to-mesenchymal transition that contributes to fibrosis. Since chronic inflammation has now been recognized as a significant contributing factor to tumorigenesis, it has also emerged that activation of endothelium also occurs in the tumor microenvironment. This review summarizes recent findings characterizing the molecular and cellular changes in the vascular endothelium that contribute to tissue fibrosis, and potentially to cancer formation.

Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ascorbic Acid ◽  
Coronary Artery ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Culture Media ◽  
Cytokine Secretion ◽  
Human Coronary Artery ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

scholarly journals From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2278
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Mahdi Abdoli Shadbad ◽  
Niloufar Sadat Nourbakhsh ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Development ◽  
Immune Checkpoints ◽  
Single Cell Sequencing ◽  
Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

scholarly journals 492 Integration of high dimensional datasets in an immunocompetent mammary mouse model reveals pathways of tolerance and resistance to immune checkpoint blockade

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A528-A528
Author(s):  
Lin Ma ◽  
Jian-Hua Mao ◽  
Mary Helen Barcellos-Hoff ◽  
Jade Moore
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Systemic Disease ◽  
Ct Imaging ◽  
High Dimensional ◽  
Cytokine Signaling ◽  
Immune Infiltrate ◽  
Pet Ct

BackgroundCheckpoint inhibitors can induce robust and durable responses in a subset of patients. Extending this benefit to more patients could be facilitated by better understanding of how interacts with immune cells with the tumor microenvironment, which is a critical barrier to control both local and systemic disease. The composition and pattern of the immune infiltrate associates with the likelihood of response to immunotherapy. Inflamed tumors that exhibit a brisk immune cell infiltrate are responsive, while those in which immune cells are completely or partially excluded are not. Transforming growth factor β (TGFβ) is immunosuppressive and associated with the immune excluded phenotype.MethodsUsing an immune competent mammary tumor derived transplant (mTDT) model recently developed in our lab, exhibits inflamed, excluded or deserts immune infiltrate phenotypes based on localization of CD8 lymphocytes. Using whole transcriptome deep sequencing, cytof, and PET-CT imaging, we evaluated the tumor, microenvironment, and immune pathway activation among immune infiltrate phenotypes.ResultsThree distinct inflamed tumors phenotypes were identified: ‘classically’ inflamed characterized by pathway evidence of increased CD8+ T cells and decreased PD-L1 expression, inflamed tumors with pathways indicative of neovascularization and STAT3 signaling and reduced T cell mobilization, and an inflamed tumor with increased immunosuppressive myeloid phenotypes. Excluded tumors were characterized by TGFβ gene expression and pro-inflammatory cytokine signaling (e.g. TNFα, IL1β), associated with decreased leukocytes homing and increased immune cell death of cells. We visualized and quantified TGFβ activity using PET-CT imaging of 89Zr-fresolimumab, a TGFβ neutralizing antibody. TGFβ activity was significantly increased in excluded tumors compared to inflamed or desert tumors, which was supported by quantitative pathology (Perkin Elmer) of its canonical signaling target, phosphorylated SMAD2 (pSMAD2). pSMAD2 was positively correlated with PD-L1 expression in the stroma of excluded tumors. In contrast, in inflamed tumors, TGFβ activity positively correlated with increased F4/80 positive macrophages and negatively correlated with expression of PD-L1. CyTOF analysis of tumor and spleen immune phenotypes revealed increased trafficking of myeloid cells in mice bearing inflamed tumors compared to excluded and deserts.ConclusionsThe immunocompetent mTDT provides a model that bridges the gap between the immune landscape and tumor microenvironment. Integration of these high-dimensional data with further studies of response to immunotherapies will help to identify tumor features that favor response to treatment or the means to convert those that are unresponsive.

Pathological Alternations of Mediastinal Fat-Associated Lymphoid Cluster and Lung in a Streptozotocin-Induced Diabetic Mouse Model

2020 ◽  
pp. 1-14
Author(s):  
Yaser H.A. Elewa ◽  
Osamu Ichii ◽  
Teppei Nakamura ◽  
Yasuhiro Kon
Keyword(s):  
Endothelial Cells ◽  
Lung Injury ◽  
Mouse Model ◽  
Immune Cells ◽  
Inflammatory Markers ◽  
Inflammatory Marker ◽  
Diabetic Mouse ◽  
Control Group ◽  
Injury Progression

Diabetes is a devastating global health problem and is considered a predisposing factor for lung injury progression. Furthermore, previous reports of the authors revealed the role of mediastinal fat-associated lymphoid clusters (MFALCs) in advancing respiratory diseases. However, no reports concerning the role of MFALCs on the development of lung injury in diabetes have been published. Therefore, this study aimed to examine the correlations between diabetes and the development of MFALCs and the progression of lung injury in a streptozotocin-induced diabetic mouse model. Furthermore, immunohistochemical analysis for immune cells (CD3+ T-lymphocytes, B220+ B-lymphocytes, Iba1+ macrophages, and Gr1+ granulocytes), vessels markers (CD31+ endothelial cells and LYVE-1+ lymphatic vessels “LVs”), and inflammatory markers (TNF-α and IL-5) was performed. In comparison to the control group, the diabetic group showed lung injury development with a significant increase in MFALC size, immune cells, LVs, and inflammatory marker, and a considerable decrease of CD31+ endothelial cells in both lung and MFALCs was observed. Furthermore, the blood glucose level showed significant positive correlations with MFALCs size, lung injury, immune cells, inflammatory markers, and LYVE-1+ LVs in lungs and MFALCs. Thus, we suggest that the development of MFALCs and LVs could contribute to lung injury progression in diabetic conditions.

scholarly journals The dynamic behavior of lipid droplets in the pre-metastatic niche

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chunliang Shang ◽  
Jie Qiao ◽  
Hongyan Guo
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Lipid Droplets ◽  
Metastatic Tumor ◽  
Current Evidence ◽  
Biological Functions ◽  
Metastatic Niche ◽  
Niche Formation

AbstractThe pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.

scholarly journals A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture.

1991 ◽  
Vol 114 (3) ◽  
pp. 557-565 ◽  
Author(s):  
K Miyake ◽  
K Medina ◽  
K Ishihara ◽  
M Kimoto ◽  
R Auerbach ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Cell Adhesion Molecule ◽  
B Lymphocyte ◽  
Murine Bone Marrow

Two new mAbs (M/K-1 and M/K-2) define an adhesion molecule expressed on stromal cell clones derived from murine bone marrow. The protein is similar in size to a human endothelial cell adhesion molecule known as VCAM-1 or INCAM110. VCAM-1 is expressed on endothelial cells in inflammatory sites and recognized by the integrin VLA-4 expressed on lymphocytes and monocytes. The new stromal cell molecule is a candidate ligand for the VLA-4 expressed on immature B lineage lymphocytes and a possible homologue of human VCAM-1. We now report additional similarities in the distribution, structure, and function of these proteins. The M/K antibodies detected large cells in normal bone marrow, as well as rare cells in other tissues. The antigen was constitutively expressed and functioned as a cell adhesion molecule on cultured murine endothelial cells. It correlated with the presence of mRNA which hybridized to a human VCAM-1 cDNA probe. Partial NH2 terminal amino acid sequencing of the murine protein revealed similarities to VCAM-1 and attachment of human lymphoma cells to murine endothelial cell lines was inhibited by the M/K antibodies. All of these observations suggest that the murine and human cell adhesion proteins may be related. The antibodies selectively interfered with B lymphocyte formation when included in long term bone marrow cultures. Moreover, they caused rapid detachment of lymphocytes from the adherent layer when added to preestablished cultures. The VCAM-like cell adhesion molecule on stromal cells and VLA-4 on lymphocyte precursors may both be important for B lymphocyte formation.

Endothelial Cell-Immune Cell Interaction in IBD

2016 ◽  
Vol 34 (1-2) ◽  
pp. 43-50 ◽  
Author(s):  
Silvio Danese ◽  
Claudio Fiocchi
Keyword(s):  
Endothelial Cells ◽  
Immune Cells ◽  
Bowel Wall ◽  
Regulatory Mechanism ◽  
Immune Cell ◽  
Cell Interaction ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Inflammatory Bowel ◽  
Lymphatic Fluid

The proper delivery of immune cells throughout the host's various tissues and organs is essential to health, and abnormalities in the type and quantity of leukocyte distribution is usually associated with disease. Because of its size and presence of a very large amount of immunocytes in the mucosa and mesenteric lymph nodes, the gut is the recipient of a constant influx of leukocytes, a process tightly regulated by multiple factors. These include cell adhesion molecules on the leukocytes and their counter-receptors on the microvascular endothelial cells in the bowel wall, a number of chemokines and cytokines that help attracting immune cells, platelets, bacterial products, danger signals, the size of the vascular and lymphatic beds and the process of leukocyte exit and circulation in the blood and lymphatic fluid. The disruption of any of the above regulatory mechanism can lead to inflammation, as is the case for inflammatory bowel disease. Learning how leukocyte and endothelial cells mutually function in health and what goes wrong in inflammation offers the opportunity to intervene therapeutically and re-establish the normal crosstalk between leukocytes and endothelial cells.

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