scholarly journals Interleukin-34 promotes tumorigenic signals for colon cancer cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Eleonora Franzè ◽  
Irene Marafini ◽  
Edoardo Troncone ◽  
Silvia Salvatori ◽  
Giovanni Monteleone
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Colon Carcinogenesis ◽  
Cell Types ◽  
Western World ◽  
Cancer Associated Fibroblasts ◽  
Colon Cancer Cells ◽  
Growth And Survival ◽  
And Function

AbstractColorectal carcinoma (CRC) is one of the most common forms of malignancy in the Western world. Accumulating evidence indicates that colon carcinogenesis is tightly controlled by tumour-associated immune cells and stromal cells, which can either stimulate or suppress CRC cell growth and survival, mainly via the production of cytokines. Interleukin-34 (IL-34), a cytokine known to regulate mainly monocyte/macrophage survival and function, is highly produced within the CRC microenvironment by several cell types, including cancer cells, tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), and regulates the pro-tumoural functions of such cells. In this article, we summarize the available data supporting the multiple effects of IL-34 in human CRC.

scholarly journals Integrin Regulation of CAF Differentiation and Function

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 715 ◽  
Author(s):  
C. Michael DiPersio ◽  
Livingston Van De Water
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Extensive Literature ◽  
Cancer Associated Fibroblasts ◽  
Epithelial Tumor ◽  
And Function

Extensive remodeling of the extracellular matrix, together with paracrine communication between tumor cells and stromal cells, contribute to an “activated” tumor microenvironment that supports malignant growth and progression. These stromal cells include inflammatory cells, endothelial cells, and cancer-associated fibroblasts (CAFs). Integrins are expressed on all tumor and stromal cell types where they regulate both cell adhesion and bidirectional signal transduction across the cell membrane. In this capacity, integrins control pro-tumorigenic cell autonomous functions such as growth and survival, as well as paracrine crosstalk between tumor cells and stromal cells. The myofibroblast-like properties of cancer-associated fibroblasts (CAFs), such as robust contractility and extracellular matrix (ECM) deposition, allow them to generate both chemical and mechanical signals that support invasive tumor growth. In this review, we discuss the roles of integrins in regulating the ability of CAFs to generate and respond to extracellular cues in the tumor microenvironment. Since functions of specific integrins in CAFs are only beginning to emerge, we take advantage of a more extensive literature on how integrins regulate wound myofibroblast differentiation and function, as some of these integrin functions are likely to extrapolate to CAFs within the tumor microenvironment. In addition, we discuss the roles that integrins play in controlling paracrine signals that emanate from epithelial/tumor cells to stimulate fibroblasts/CAFs.

scholarly journals Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

2020 ◽  
Vol 21 (24) ◽  
pp. 9585
Author(s):  
Melania Dovizio ◽  
Patrizia Ballerini ◽  
Rosa Fullone ◽  
Stefania Tacconelli ◽  
Annalisa Contursi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Immune Cells ◽  
Expression Patterns ◽  
Cell Communication ◽  
Antiplatelet Agents ◽  
Cell Types ◽  
Disease Monitoring ◽  
Crucial Component ◽  
Numerous Cell

Platelets contribute to several types of cancer through plenty of mechanisms. Upon activation, platelets release many molecules, including growth and angiogenic factors, lipids, and extracellular vesicles, and activate numerous cell types, including vascular and immune cells, fibroblasts, and cancer cells. Hence, platelets are a crucial component of cell–cell communication. In particular, their interaction with cancer cells can enhance their malignancy and facilitate the invasion and colonization of distant organs. These findings suggest the use of antiplatelet agents to restrain cancer development and progression. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer-patient platelets show specific proteomic and transcriptomic expression patterns, a phenomenon called tumor-educated platelets (TEP). The transcriptomic/proteomic profile of platelets can provide information for the early detection of cancer and disease monitoring. Platelet ability to interact with tumor cells and transfer their molecular cargo has been exploited to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity often associated with traditional chemotherapy. Platelets are extraordinary cells with many functions whose exploitation will improve cancer diagnosis and treatment.

scholarly journals When Cells Suffocate: Autophagy in Cancer and Immune Cells under Low Oxygen

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Katrin Schlie ◽  
Jaeline E. Spowart ◽  
Luke R. K. Hughson ◽  
Katelin N. Townsend ◽  
Julian J. Lum
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Patient Treatment ◽  
Low Oxygen ◽  
Tumor Environment ◽  
And Function ◽  
The Impact

Hypoxia is a signature feature of growing tumors. This cellular state creates an inhospitable condition that impedes the growth and function of all cells within the immediate and surrounding tumor microenvironment. To adapt to hypoxia, cells activate autophagy and undergo a metabolic shift increasing the cellular dependency on anaerobic metabolism. Autophagy upregulation in cancer cells liberates nutrients, decreases the buildup of reactive oxygen species, and aids in the clearance of misfolded proteins. Together, these features impart a survival advantage for cancer cells in the tumor microenvironment. This observation has led to intense research efforts focused on developing autophagy-modulating drugs for cancer patient treatment. However, other cells that infiltrate the tumor environment such as immune cells also encounter hypoxia likely resulting in hypoxia-induced autophagy. In light of the fact that autophagy is crucial for immune cell proliferation as well as their effector functions such as antigen presentation and T cell-mediated killing of tumor cells, anticancer treatment strategies based on autophagy modulation will need to consider the impact of autophagy on the immune system.

scholarly journals Invasive Colon Cancer Cells Induce Transdifferentiation of Endothelium to Cancer-Associated Fibroblasts through Microtubules Enriched in Tubulin-β3

2018 ◽  
Vol 20 (1) ◽  
pp. 53 ◽  
Author(s):  
Marta Wawro ◽  
Katarzyna Chojnacka ◽  
Katarzyna Wieczorek-Szukała ◽  
Katarzyna Sobierajska ◽  
Jolanta Niewiarowska
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Associated Fibroblasts ◽  
Colon Cancer Cells ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Cytoskeleton Reorganization ◽  
Advanced Stages ◽  
Endothelial To Mesenchymal Transition ◽  
And Migration

Colon cancer, the second leading cause of cancer-related deaths in the world, is usually diagnosed in invasive stages. The interactions between cancer cells and cells located in their niche remain the crucial mechanism inducing tumor metastasis. The most important among those cells are cancer-associated fibroblasts (CAFs), the heterogeneous group of myofibroblasts transdifferentiated from numerous cells of different origin, including endothelium. The endothelial-to-mesenchymal transition (EndMT) is associated with modulation of cellular morphology, polarization and migration ability as a result of microtubule cytoskeleton reorganization. Here we reveal, for the first time, that invasive colon cancer cells regulate EndMT of endothelium via tubulin-β3 upregulation and its phosphorylation. Thus, we concluded that therapies based on inhibition of tubulin-β3 expression or phosphorylation, or blocking tubulin-β3’s recruitment to the microtubules, together with anti-inflammatory chemotherapeutics, are promising means to treat advanced stages of colon cancer.

scholarly journals Single cell analysis reveals immune cell–adipocyte crosstalk regulating the transcription of thermogenic adipocytes

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Prashant Rajbhandari ◽  
Douglas Arneson ◽  
Sydney K Hart ◽  
In Sook Ahn ◽  
Graciel Diamante ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Metabolic Response ◽  
Cell Types ◽  
Specific Cell ◽  
Beneficial Effects ◽  
Thermogenic Adipocytes ◽  
And Function

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.

scholarly journals Epithelial–mesenchymal transition and metastasis of colon cancer cells induced by the FAK pathway in cancer-associated fibroblasts

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052093124
Author(s):  
Xuefeng Xuefeng ◽  
Ming-Xing Hou ◽  
Zhi-Wen Yang ◽  
Agudamu Agudamu ◽  
Feng Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
3D Culture ◽  
Cancer Associated Fibroblasts ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Lovo Cells ◽  
Related Proteins

Objective The role and mechanism of tetrathiomolybdate (TM) in cancer-associated fibroblasts (CAFs) in colon cancer using three-dimensional (3D) culture were investigated, and the associations between the focal adhesion kinase (FAK) pathway and epithelial–mesenchymal transition (EMT) in CAFs were explored. Methods A 3D co-culture model of colon cancer LOVO cells with CAFs and normal fibroblasts (NFs) was established using Matrigel as a scaffold material. The differential expression of LOXL2 (lysyl oxidase-like 2) in the supernatant of CAFs and NFs was determined using ELISA, and expression levels of EMT-related proteins and FAK signaling pathway-related proteins were determined using western blot. Results LOXL2 levels secreted by CAFs were higher compared with that secreted by NFs. In the CAF + LOVO group, compared with the LOVO group, E-cadherin expression decreased significantly, while N-cadherin and F-PAK expression increased significantly. TM results were opposite compared with the above results. Conclusions CAFs stimulate EMT in human colon cancer LOVO cells by secreting LOXL2 to activate the FAK signaling pathway, thereby promoting tumor metastasis. TM inhibited the occurrence of EMT in the CAF-induced colon cancer LOVO cell line, thereby reducing the invasion and metastasis of colon cancer cells.

scholarly journals Mesenchymal Stromal-Like Cells in the Glioma Microenvironment: What Are These Cells?

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2628
Author(s):  
Anne Clavreul ◽  
Philippe Menei
Keyword(s):  
Blood Vessels ◽  
Immune Cells ◽  
Stromal Cells ◽  
Low Ph ◽  
Cancer Associated Fibroblasts ◽  
Tumor Resistance ◽  
Interstitial Pressure ◽  
Close Proximity ◽  
Cellular Components ◽  
Glioma Microenvironment

The glioma microenvironment is a critical regulator of tumor progression. It contains different cellular components such as blood vessels, immune cells, and neuroglial cells. It also contains non-cellular components, such as the extracellular matrix, extracellular vesicles, and cytokines, and has certain physicochemical properties, such as low pH, hypoxia, elevated interstitial pressure, and impaired perfusion. This review focuses on a particular type of cells recently identified in the glioma microenvironment: glioma-associated stromal cells (GASCs). This is just one of a number of names given to these mesenchymal stromal-like cells, which have phenotypic and functional properties similar to those of mesenchymal stem cells and cancer-associated fibroblasts. Their close proximity to blood vessels may provide a permissive environment, facilitating angiogenesis, invasion, and tumor growth. Additional studies are required to characterize these cells further and to analyze their role in tumor resistance and recurrence.

scholarly journals Colon Cancer and Perturbations of the Sphingolipid Metabolism

2019 ◽  
Vol 20 (23) ◽  
pp. 6051 ◽  
Author(s):  
Miroslav Machala ◽  
Jiřina Procházková ◽  
Jiřina Hofmanová ◽  
Lucie Králiková ◽  
Josef Slavík ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Colon ◽  
Sphingolipid Metabolism ◽  
Western World ◽  
Colon Cancer Cells ◽  
Colon Tumors ◽  
Metabolism Enzymes

The development and progression of colon cancer (CRC), a major cause of cancer-related death in the western world, is accompanied with alterations of sphingolipid (SL) composition in colon tumors. A number of enzymes involved in the SL metabolism have been found to be deregulated in human colon tumors, in experimental rodent studies, and in human colon cancer cells in vitro. Therefore, the enzymatic pathways that modulate SL levels have received a significant attention, due to their possible contribution to CRC development, or as potential therapeutic targets. Many of these enzymes are associated with an increased sphingosine-1-phosphate/ceramide ratio, which is in turn linked with increased colon cancer cell survival, proliferation and cancer progression. Nevertheless, more attention should also be paid to the more complex SLs, including specific glycosphingolipids, such as lactosylceramides, which can be also deregulated during CRC development. In this review, we focus on the potential roles of individual SLs/SL metabolism enzymes in colon cancer, as well as on the pros and cons of employing the current in vitro models of colon cancer cells for lipidomic studies investigating the SL metabolism in CRC.

scholarly journals Transforming Growth Factor-β Signaling in Fibrotic Diseases and Cancer-Associated Fibroblasts

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1666
Author(s):  
Xueke Shi ◽  
Christian D. Young ◽  
Hongmei Zhou ◽  
Xiao-Jing Wang
Keyword(s):  
Growth Factor ◽  
Cancer Progression ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Cancer Associated Fibroblasts ◽  
The Matrix ◽  
Fibrotic Diseases ◽  
Fibrotic Disorders

Transforming growth factor-β (TGF-β) signaling is essential in embryo development and maintaining normal homeostasis. Extensive evidence shows that TGF-β activation acts on several cell types, including epithelial cells, fibroblasts, and immune cells, to form a pro-fibrotic environment, ultimately leading to fibrotic diseases. TGF-β is stored in the matrix in a latent form; once activated, it promotes a fibroblast to myofibroblast transition and regulates extracellular matrix (ECM) formation and remodeling in fibrosis. TGF-β signaling can also promote cancer progression through its effects on the tumor microenvironment. In cancer, TGF-β contributes to the generation of cancer-associated fibroblasts (CAFs) that have different molecular and cellular properties from activated or fibrotic fibroblasts. CAFs promote tumor progression and chronic tumor fibrosis via TGF-β signaling. Fibrosis and CAF-mediated cancer progression share several common traits and are closely related. In this review, we consider how TGF-β promotes fibrosis and CAF-mediated cancer progression. We also discuss recent evidence suggesting TGF-β inhibition as a defense against fibrotic disorders or CAF-mediated cancer progression to highlight the potential implications of TGF-β-targeted therapies for fibrosis and cancer.

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