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 Regulation of prostate cancer progression by the tumor microenvironment

2016 ◽  
Vol 380 (1) ◽  
pp. 340-348 ◽  
Author(s):  
Stephen L. Shiao ◽  
Gina Chia-Yi Chu ◽  
Leland W.K. Chung
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Prostate Cancer Progression

scholarly journals Repression of MUC1 promotes expansion and suppressive function of myeloid-derived suppressor cells in pancreatic ductal adenocarcinoma and breast cancer murine models

2020 ◽  
Author(s):  
S. Mahnaz ◽  
L. Das Roy ◽  
M. Bose ◽  
C. De ◽  
S. Nath ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathways ◽  
Suppressor Cells ◽  
Ductal Adenocarcinoma ◽  
Myeloid Derived Suppressor Cells ◽  
Mucin 1 ◽  
Transmembrane Glycoprotein ◽  
The Impact

ABSTRACTMyeloid-derived suppressor cells (MDSCs) are immature myeloid cells that are responsible for immunosuppression in tumor microenvironment. Here we report the impact of mucin 1 (MUC1), a transmembrane glycoprotein, on proliferation and functional activity of MDSCs. To determine the role of MUC1 in MDSC phenotype, we analyzed MDSCs derived from wild type (WT) and MUC1-knockout (MUC1KO) mice bearing pancreatic ductal adenocarcinoma KCKO and breast cancer C57MG xenografts. We observed enhanced tumor growth in MUC1KO mice compared to WT mice in both pancreatic KCKO and breast C57MG cancer models due to increased MDSC population and enrichment of Tregs in tumor microenvironment. Our current study shows that knockdown of MUC1 in MDSCs promotes proliferation and immature suppressive phenotype indicated by increased level of iNOS, ARG1 activity and TGF-β secretion under cancer conditions. Increased activity of MDSCs leads to repression of IL-2 and IFN-ɣ production by T-cells. We were able to find that MDSCs from MUC1KO mice have higher levels of c-Myc and activated pSTAT3 as compared to MUC1 WT mice, that are signaling pathways leading to increased survival, proliferation and prevention of maturation. In summary, MUC1 regulates signaling pathways that maintain immunosuppressive properties of MDSCs. Thus, immunotherapy must target only tumor associated MUC1 on epithelial cells and not MUC1 on hematopoietic cells to avoid expansion and suppressive functions of MDSC.

scholarly journals Main Inflammatory Cells and Potentials of Anti-Inflammatory Agents in Prostate Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1153 ◽  
Author(s):  
Takuji Hayashi ◽  
Kazutoshi Fujita ◽  
Makoto Matsushita ◽  
Norio Nonomura
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Immune Cells ◽  
Acquired Resistance ◽  
Suppressor Cells ◽  
Basic Research ◽  
Inflammatory Cells ◽  
Intercellular Signaling ◽  
Prostate Cancer Progression ◽  
Anti Inflammatory

Prostate cancer is the most common type of cancer and the leading cause of cancer deaths among men in many countries. Preventing progression is a major concern for prostate cancer patients on active surveillance, patients with recurrence after radical therapies, and patients who acquired resistance to systemic therapies. Inflammation, which is induced by various factors such as infection, microbiome, obesity, and a high-fat diet, is the major etiology in the development of prostate cancer. Inflammatory cells play important roles in tumor progression. Various immune cells including tumor-associated neutrophils, tumor-infiltrating macrophages, myeloid-derived suppressor cells, and mast cells promote prostate cancer via various intercellular signaling. Further basic studies examining the relationship between the inflammatory process and prostate cancer progression are warranted. Interventions by medications and diets to control systemic and/or local inflammation might be effective therapies for prostate cancer progression. Epidemiological investigations and basic research using human immune cells or mouse models have revealed that non-steroidal anti-inflammatory drugs, metformin, statins, soy isoflavones, and other diets are potential interventions for preventing progression of prostate cancer by suppressing inflammation. It is essential to evaluate appropriate indications and doses of each drug and diet.

scholarly journals Castration-mediated IL-8 Promotes Myeloid Infiltration and Prostate Cancer Progression

2019 ◽  
Author(s):  
Zoila A. Lopez-Bujanda ◽  
Michael C. Haffner ◽  
Matthew G. Chaimowitz ◽  
Nivedita Chowdhury ◽  
Nicholas J. Venturini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Suppressor Cells ◽  
Immune Checkpoint Blockade ◽  
Prostate Cancer Progression ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Intrinsic Factors ◽  
Castration Resistant ◽  
Clinical Responses

SummaryImmunotherapy is a treatment for many types of cancer, primarily due to deep and durable clinical responses mediated by immune checkpoint blockade (ICB)1, 2. Prostate cancer is a notable exception in that it is generally unresponsive to ICB. The standard treatment for advanced prostate cancer is androgen-deprivation therapy (ADT), a form of castration (CTX). ADT is initially effective, but over time patients eventually develop castration-resistant prostate cancer (CRPC). Here, we focused on defining tumor-cell intrinsic factors that contribute to prostate cancer progression and resistance to immunotherapy. We analyzed cancer cells isolated from castration-sensitive and castration-resistant prostate tumors, and discovered that castration resulted in significant secretion of Interleukin-8 (IL-8) and it’s likely murine homolog Cxcl15. These chemokines drove subsequent intra-tumoral infiltration with polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), promoting tumor progression. PMN-MDSC infiltration was abrogated when IL-8 was deleted from prostate cancer epithelial cells using CRISPR/Cas9, or when PMN-MDSC migration was blocked with antibodies against the IL-8 receptor CXCR2. Blocking PMN-MDSC infiltration in combination with anti-CTLA-4 delayed the onset of castration resistance and increased the density of polyfunctional CD8 T cells in tumors. Taken together, our findings establish castration-mediated IL-8 secretion and subsequent PMN-MDSC infiltration as a key suppressive mechanism in the progression of prostate cancer. Targeting of the IL-8/CXCR2 axis around the time of ADT, in combination with ICB, represents a novel therapeutic approach to delay prostate cancer progression to advanced disease.

scholarly journals Circular RNA circANKS1B as the Sponge of miR-152-3p Promotes Prostate Cancer Progression by up-Regulating TGF-α Expression

2020 ◽  
Author(s):  
Liangjun Tao ◽  
Xinyuan Pan ◽  
Jiawei Wang ◽  
Li Zhang ◽  
Lingsong Tao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Prostate Cancer Progression ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
And Function ◽  
The Impact

Abstract Background: Growing studies indicate that circRNAs play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aims to investigate the expression and function of circANKS1B in prostate cancer (PC).Methods: The expression of circANKS1B and miRNA-152-3p were determined by real-time qRT-PCR. The cell migration and invasion were measured by transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by dual-luciferase reporter gene assay. Rescue experiments were conducted to demonstrate whether circANKS1B regulated the migration and invasion of PC cells by the circANKS1B-miR-152-3p-TGF-α pathway.Results: The expression of circANKS1B was dramatically up-regulated both in PC cells and tissues. Moreover, high circANKS1B expression was associated with a poor prognosis of PC patients. Dual-luciferase reporter assay indicated that circABKS1B directly bound to miRNA-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B remarkably suppressed PC cells invasion and TGF-α expression, while the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on PC cell invasion was also abrogated by TGF-α deficiency. In all, circANKS1B as the sponge of miR-152-3p promotes prostate cancer progression by up-regulating TGF-α expression.Conclusion: Our findings reveal that circANKS1B could be a potential prognostic biomarker and therapeutic target of PC.

scholarly journals The impact of age on prostate cancer progression and quality of life in active surveillance patients

BJUI Compass ◽  
2020 ◽  
Author(s):  
Gregory S. Merrick ◽  
Gabe Rohmann ◽  
Robert Galbreath ◽  
Whitney Scholl ◽  
Ryan Fiano ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Active Surveillance ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
The Impact

scholarly journals Prognostic Value of CD1B in Localised Prostate Cancer

2019 ◽  
Vol 16 (23) ◽  
pp. 4723 ◽  
Author(s):  
Cheng-Hsueh Lee ◽  
Lih-Chyang Chen ◽  
Chia-Cheng Yu ◽  
Wen-Hsin Lin ◽  
Victor C. Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Cell Types ◽  
Regulatory Elements ◽  
Marker Genes ◽  
Nucleotide Polymorphisms ◽  
Prostate Cancer Progression ◽  
Transcriptional Regulatory Elements ◽  
Haematopoietic Cell ◽  
The Impact

Cluster of differentiation (CD) antigens are cell surface markers used to differentiate haematopoietic cell types. These antigens are present in various malignancies and are reportedly linked to patient prognosis; however, they have not been implemented as prostate cancer progression markers. Here, we aimed to assess the impact of genetic variation in haematopoietic cell CD markers on clinical outcomes in patients with prostate cancer. An association study of 458 patients with prostate cancer was conducted to identify single-nucleotide polymorphisms in 11 candidate CD marker genes associated with biochemical recurrence (BCR) after radical prostatectomy. Identified predictors were further evaluated in an additional cohort of 185 patients. Joint population analyses showed that CD1B rs3181082 is associated with BCR (adjusted hazard ratio 1.42, 95% confidence interval 1.09–1.85, p = 0.010). In addition, rs3181082 overlapped with predicted transcriptional regulatory elements and affected CD1B expression. Furthermore, low CD1B expression correlated with poorer BCR-free survival. Our results indicated that CD1B rs3181082 confers prostate cancer progression and may help improve clinical prognostic stratification.

scholarly journals The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 210
Author(s):  
Maximilian Haist ◽  
Henner Stege ◽  
Stephan Grabbe ◽  
Matthias Bros
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
T Cell Activation ◽  
Metastatic Cancer ◽  
Suppressor Cells ◽  
Cell Populations ◽  
Myeloid Derived Suppressor Cells ◽  
Immunosuppressive Cell ◽  
The Impact

Immune checkpoint inhibitors (ICI) have led to profound and durable tumor regression in some patients with metastatic cancer diseases. However, many patients still do not derive benefit from immunotherapy. Here, the accumulation of immunosuppressive cell populations within the tumor microenvironment (TME), such as myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), and regulatory T cells (Treg), contributes to the development of immune resistance. MDSC and Treg expand systematically in tumor patients and inhibit T cell activation and T effector cell function. Numerous studies have shown that the immunosuppressive mechanisms exerted by those inhibitory cell populations comprise soluble immunomodulatory mediators and receptor interactions. The latter are also required for the crosstalk of MDSC and Treg, raising questions about the relevance of cell–cell contacts for the establishment of their inhibitory properties. This review aims to outline the current knowledge on the crosstalk between these two cell populations, issuing particularly the potential role of cell adhesion molecules. In this regard, we further discuss the relevance of β2 integrins, which are essential for the differentiation and function of leukocytes as well as for MDSC–Treg interaction. Lastly, we aim to describe the impact of such bidirectional crosstalk for basic and applied cancer research and discuss how the targeting of these pathways might pave the way for future approaches in immunotherapy.

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