scholarly journals CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of Receptors CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 Ligands

2020 ◽  
Vol 21 (20) ◽  
pp. 7619 ◽  
Author(s):  
Jan Korbecki ◽  
Szymon Grochans ◽  
Izabela Gutowska ◽  
Katarzyna Barczak ◽  
Irena Baranowska-Bosiacka
Keyword(s):  
Endothelial Cells ◽  
Chemokine Receptors ◽  
Vascular Endothelial Cells ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Migration And Invasion ◽  
Apoptosis Resistance ◽  
Chemokine Receptor Ccr5 ◽  
Organ Specific ◽  
Cc Chemokines

CC chemokines (or β-chemokines) are 28 chemotactic cytokines with an N-terminal CC domain that play an important role in immune system cells, such as CD4+ and CD8+ lymphocytes, dendritic cells, eosinophils, macrophages, monocytes, and NK cells, as well in neoplasia. In this review, we discuss human CC motif chemokine ligands: CCL1, CCL3, CCL4, CCL5, CCL18, CCL19, CCL20, CCL21, CCL25, CCL27, and CCL28 (CC motif chemokine receptor CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 ligands). We present their functioning in human physiology and in neoplasia, including their role in the proliferation, apoptosis resistance, drug resistance, migration, and invasion of cancer cells. We discuss the significance of chemokine receptors in organ-specific metastasis, as well as the influence of each chemokine on the recruitment of various cells to the tumor niche, such as cancer-associated fibroblasts (CAF), Kupffer cells, myeloid-derived suppressor cells (MDSC), osteoclasts, tumor-associated macrophages (TAM), tumor-infiltrating lymphocytes (TIL), and regulatory T cells (Treg). Finally, we show how the effect of the chemokines on vascular endothelial cells and lymphatic endothelial cells leads to angiogenesis and lymphangiogenesis.

scholarly journals CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of the Ligands of Receptors CCR1, CCR2, CCR3, and CCR4

2020 ◽  
Vol 21 (21) ◽  
pp. 8412
Author(s):  
Jan Korbecki ◽  
Klaudyna Kojder ◽  
Donata Simińska ◽  
Romuald Bohatyrewicz ◽  
Izabela Gutowska ◽  
...  
Keyword(s):  
Physiological Function ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Myeloid Derived Suppressor Cells ◽  
Anti Cancer ◽  
Organ Specific ◽  
Cc Chemokines ◽  
Infiltrating Lymphocytes ◽  
Tumor Associated Neutrophils

CC chemokines, a subfamily of 27 chemotactic cytokines, are a component of intercellular communication, which is crucial for the functioning of the tumor microenvironment. Although many individual chemokines have been well researched, there has been no comprehensive review presenting the role of all known human CC chemokines in the hallmarks of cancer, and this paper aims at filling this gap. The first part of this review discusses the importance of CCL1, CCL3, CCL4, CCL5, CCL18, CCL19, CCL20, CCL21, CCL25, CCL27, and CCL28 in cancer. Here, we discuss the significance of CCL2 (MCP-1), CCL7, CCL8, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL22, CCL23, CCL24, and CCL26. The presentation of each chemokine includes its physiological function and then the role in tumor, including proliferation, drug resistance, migration, invasion, and organ-specific metastasis of tumor cells, as well as the effects on angiogenesis and lymphangiogenesis. We also discuss the effects of each CC chemokine on the recruitment of cancer-associated cells to the tumor niche (eosinophils, myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), regulatory T cells (Treg)). On the other hand, we also present the anti-cancer properties of CC chemokines, consisting in the recruitment of tumor-infiltrating lymphocytes (TIL).

scholarly journals The Chemokine Receptor D6 Constitutively Traffics to and from the Cell Surface to Internalize and Degrade Chemokines

2004 ◽  
Vol 15 (5) ◽  
pp. 2492-2508 ◽  
Author(s):  
Michele Weber ◽  
Emma Blair ◽  
Clare V. Simpson ◽  
Maureen O'Hara ◽  
Paul E. Blackburn ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Membrane Protein ◽  
Cell Surface ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Lymphatic Endothelial Cells ◽  
Recycling Endosomes ◽  
High Affinity ◽  
Cc Chemokines ◽  
Cc Chemokine Receptor 5

The D6 heptahelical membrane protein, expressed by lymphatic endothelial cells, is able to bind with high affinity to multiple proinflammatory CC chemokines. However, this binding does not allow D6 to couple to the signaling pathways activated by typical chemokine receptors such as CC-chemokine receptor-5 (CCR5). Here, we show that D6, like CCR5, can rapidly internalize chemokines. However, D6-internalized chemokines are more effectively retained intracellularly because they more readily dissociate from the receptor during vesicle acidification. These chemokines are then degraded while the receptor recycles to the cell surface. Interestingly, D6-mediated chemokine internalization occurs without bringing about a reduction in cell surface D6 levels. This is possible because unlike CCR5, D6 is predominantly localized in recycling endosomes capable of trafficking to and from the cell surface in the absence of ligand. When chemokine is present, it can enter the cells associated with D6 already destined for internalization. By this mechanism, D6 can target chemokines for degradation without the necessity for cell signaling, and without desensitizing the cell to subsequent chemokine exposure.

scholarly journals Single-cell RNA-seq reveals lineage-specific regulatory changes of fibroblasts and vascular endothelial cells in keloid

2020 ◽  
Author(s):  
Xuanyu Liu ◽  
Wen Chen ◽  
Meng Yuan ◽  
Zhujun Li ◽  
Tian Meng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Single Cell ◽  
Transforming Growth Factor ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Rna Seq ◽  
Apoptosis Resistance ◽  
Cell Lineages ◽  
Medical Therapies ◽  
Keloid Fibroblasts

AbstractKeloid is a benign dermal fibrotic disorder with some features similar to malignant tumors such as hyper-proliferation, apoptosis resistance and invasion. keloid remains a therapeutic challenge in terms of high recurrence rate and lack of satisfactory medical therapies, which is partially due to the incomplete understanding of keloid pathogenesis. A thorough understanding of the cellular and molecular mechanism of keloid pathogenesis would facilitate the development of novel medical therapies for this disease. Here, we performed single-cell RNA-seq of 28,064 cells from keloid skin tissue and adjacent relatively normal tissue. Unbiased clustering revealed substantial cellular heterogeneity of the keloid tissue, which included 21 cell clusters assigned to 11 cell lineages. Differential proportion analysis revealed significant expansion for fibroblasts and vascular endothelial cells in keloid compared with control, reflecting their strong association with keloid pathogenesis. We then identified five previously unrecognized subpopulations of keloid fibroblasts and four subpopulations of vascular endothelial cells. Comparative analyses were performed to identify the dysregulated pathways, regulators and ligand-receptor interactions for keloid fibroblasts and vascular endothelial cells, the two important cell lineages in keloid pathogenesis and for medical interventions. Our results highlight the roles of transforming growth factor beta and Eph-ephrin signaling pathways in both the aberrant fibrogenesis and angiogenesis of keloid. Critical regulators and signaling receptors implicated in the fibrogenesis of other fibrotic disorders, such as TWIST1, FOXO3, SMAD3 and EPHB2, ranked at the top in the regulatory network of keloid fibroblasts. In addition, tumor-related pathways such as negative regulation of PTEN transcription were found to be activated in keloid fibroblasts and vascular endothelial cells, which may be responsible for the malignant features of keloid. Our study put novel insights into the pathogenesis of keloid, and provided potential targets for medical therapies. Our dataset also constitutes a valuable resource for further investigations of the mechanism of keloid pathogenesis.

scholarly journals Fractalkine/CX3CL1 in Neoplastic Processes

2020 ◽  
Vol 21 (10) ◽  
pp. 3723 ◽  
Author(s):  
Jan Korbecki ◽  
Donata Simińska ◽  
Klaudyna Kojder ◽  
Szymon Grochans ◽  
Izabela Gutowska ◽  
...  
Keyword(s):  
Spinal Metastasis ◽  
Growth Factor Receptor ◽  
Suppressor Cells ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion ◽  
Apoptosis Resistance ◽  
Neoplastic Processes ◽  
Chemokine Ligand ◽  
And Migration

Fractalkine/CX3C chemokine ligand 1 (CX3CL1) is a chemokine involved in the anticancer function of lymphocytes—mainly NK cells, T cells and dendritic cells. Its increased levels in tumors improve the prognosis for cancer patients, although it is also associated with a poorer prognosis in some types of cancers, such as pancreatic ductal adenocarcinoma. This work focuses on the ‘hallmarks of cancer’ involving CX3CL1 and its receptor CX3CR1. First, we describe signal transduction from CX3CR1 and the role of epidermal growth factor receptor (EGFR) in this process. Next, we present the role of CX3CL1 in the context of cancer, with the focus on angiogenesis, apoptosis resistance and migration and invasion of cancer cells. In particular, we discuss perineural invasion, spinal metastasis and bone metastasis of cancers such as breast cancer, pancreatic cancer and prostate cancer. We extensively discuss the importance of CX3CL1 in the interaction with different cells in the tumor niche: tumor-associated macrophages (TAM), myeloid-derived suppressor cells (MDSC) and microglia. We present the role of CX3CL1 in the development of active human cytomegalovirus (HCMV) infection in glioblastoma multiforme (GBM) brain tumors. Finally, we discuss the possible use of CX3CL1 in immunotherapy.

scholarly journals Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

2020 ◽  
Vol 21 (16) ◽  
pp. 5647 ◽  
Author(s):  
Jan Korbecki ◽  
Klaudyna Kojder ◽  
Katarzyna Barczak ◽  
Donata Simińska ◽  
Izabela Gutowska ◽  
...  
Keyword(s):  
T Cells ◽  
Chemokine Receptors ◽  
Oxygen Deficiency ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Hypoxia Inducible Factors ◽  
Cc Chemokine ◽  
Neoplastic Processes ◽  
Cc Chemokines ◽  
The Impact

Hypoxia, i.e., oxygen deficiency condition, is one of the most important factors promoting the growth of tumors. Since its effect on the chemokine system is crucial in understanding the changes in the recruitment of cells to a tumor niche, in this review we have gathered all the available data about the impact of hypoxia on β chemokines. In the introduction, we present the chronic (continuous, non-interrupted) and cycling (intermittent, transient) hypoxia together with the mechanisms of activation of hypoxia inducible factors (HIF-1 and HIF-2) and NF-κB. Then we describe the effect of hypoxia on the expression of chemokines with the CC motif: CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL24, CCL25, CCL26, CCL27, CCL28 together with CC chemokine receptors: CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10. To better understand the effect of hypoxia on neoplastic processes and changes in the expression of the described proteins, we summarize the available data in a table which shows the effect of individual chemokines on angiogenesis, lymphangiogenesis, and recruitment of eosinophils, myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and tumor-associated macrophages (TAM) to a tumor niche.

scholarly journals Differentiation of human intestinal organoids with endogenous vascular endothelial cells

2020 ◽  
Author(s):  
Emily M. Holloway ◽  
Joshua H. Wu ◽  
Michael Czerwinkski ◽  
Caden W. Sweet ◽  
Angeline Wu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Specific Gene ◽  
Gene Signatures ◽  
Transcriptional Signature ◽  
Intestinal Organoids ◽  
Organ Systems ◽  
Organ Specific ◽  
And Function

SUMMARYHuman pluripotent stem cell (hPSC)-derived intestinal organoids (HIOs) generated using directed differentiation lack some cellular populations found in the native organ, including vasculature. Using single cell RNA sequencing (scRNAseq), we have identified a transient population of endothelial cells (ECs) present early in HIO differentiation that are lost over time in culture. Here, we have developed a method to enhance co-differentiation and maintenance of ECs within HIOs (vHIOs). Given that ECs are known to possess organ specific gene expression, morphology and function, we used bulk RNAseq and scRNAseq to interrogate the developing human intestine, lung, and kidney in order to identify organ-enriched EC-gene signatures in these organ systems. By comparing organ-specific gene signatures along with markers validated by fluorescent in situ hybridization to HIO ECs, we find that HIO ECs grown in vitro share the highest similarity with native intestinal ECs relative to kidney and lung. Together, these data show that HIOs can co-differentiate a native EC population that are properly patterned with an intestine-specific EC transcriptional signature in vitro.

scholarly journals The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature

2021 ◽  
Vol 22 (2) ◽  
pp. 843
Author(s):  
Jan Korbecki ◽  
Klaudyna Kojder ◽  
Patrycja Kapczuk ◽  
Patrycja Kupnicka ◽  
Barbara Gawrońska-Szklarz ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Hypoxia Inducible Factor ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Cancer Therapies ◽  
Hypoxia Inducible Factor 1 ◽  
Cxc Chemokine ◽  
Induced Changes ◽  
Available Information ◽  
Infiltrating Lymphocytes

Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors—CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8. First, we present basic information on the effect of these chemoattractant cytokines on cancer processes. We then discuss the effect of hypoxia-induced changes on CXC chemokine expression on the angiogenesis, lymphangiogenesis and recruitment of various cells to the tumor niche, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), regulatory T cells (Tregs) and tumor-infiltrating lymphocytes (TILs). Finally, the review summarizes data on the use of drugs targeting the CXC chemokine system in cancer therapies.

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