scholarly journals Fibrin and Extracellular Matrix: Scaffolds and Network for Malignant Cells

2021 ◽  
Vol 9 (9) ◽  
Author(s):  
F.W. Schardt ◽  
B. Schmausser ◽  
S. Bedel ◽  
E. Bachmann ◽  
E. Henke
Keyword(s):  
Extracellular Matrix ◽  
Immune System ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Tumor Response ◽  
Combined Therapy ◽  
Cross Linking ◽  
Malignant Cells ◽  
Positive Effects ◽  
Protective Shield

Malignant cells build up a protective shield in form of a fibrin meshwork surrounding the tumor which helps it to escape the body’s immune system. In addition, tumor and stromal cells provide with an abundant extracellular matrix (ECM) consisting of proteoglycans, collagens, glycoproteins and glucosaminoglycans an additional scaffold with the capacity to bind large quantities of immunsuppressive substances. Many investigations found that heparin has a wide variety of positive effects counteracting these shielding and immunosuppressive properties of the ECM. Heparin can bind and neutralize many protective substances produced by the tumor cells. It inhibits cross-linking of collagen by deamination, and reduces the expression of FAK, LOX, glucosamines and proteoglycans. By these actions it prevents the development of a stiff and rigid ECM which presents additionally an effective scaffold for the tumor cells and also reduce the efficiency of therapeutic methods. In an ambulant trial with exogenously-added heparin in high dosages the survival probability over three years was significantly higher than without (p<0.001). Therefore, a combined therapy with a fibrinolyticum and heparin should be considered. This auxiliary treatment has the potential to support established therapy and improve anti-tumor response by the immune system.

scholarly journals Jun-regulated genes promote interaction of diffuse large B-cell lymphoma with the microenvironment

Blood ◽  
2015 ◽  
Vol 125 (6) ◽  
pp. 981-991 ◽  
Author(s):  
Marzenna Blonska ◽  
Yifan Zhu ◽  
Hubert H. Chuang ◽  
M. James You ◽  
Kranthi Kunkalla ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
B Cell ◽  
Stromal Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Matrix Proteins ◽  
Malignant Cells ◽  
Large B Cell Lymphoma ◽  
Key Points ◽  
Large B Cell

Key Points Elevated Jun signaling promotes lymphoma growth and dissemination to extranodal sites. Jun-regulated genes mediate the interaction of malignant cells with stromal cells and adhesion to extracellular matrix proteins.

scholarly journals The Role of Extracellular Vesicles in the Progression of Tumors towards Metastasis

2021 ◽  
Author(s):  
Bhaskar Basu ◽  
Subhajit Karmakar
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Lipid Membrane ◽  
Recipient Cell ◽  
Ecm Remodeling ◽  
Secondary Tumor ◽  
Metastatic Cells

Extracellular vesicles (EVs) are cell-derived lipid membrane bound vesicles that serve as mediators of intercellular communication. EVs have been found to regulate a wide range of cellular processes through the transference of genetic, protein and lipid messages from the host cell to the recipient cell. Unsurprisingly, this major mode of intracellular communication would be abrogated in cancer. Ever increasing evidence points towards a key role of EVs in promoting tumor development and in contributing to the various stages of metastasis. Tumor released EVs have been shown to facilitate the transference of oncogenic proteins and nucleic acids to other tumor cells and to the surrounding stromal cells, thereby setting up a tumor permissive microenvironment. EVs released from tumor cells have been shown to promote extracellular matrix (ECM) remodeling through the modulation of neighboring tumor cells and stromal cells. EVs released from disseminated tumor cells have been reported to attract circulating tumor cells (CTCs) via chemotaxis and induce the production of specific extracellular matrix components from neighboring stromal cells so as to support the growth of metastatic cells at the secondary tumor site. Circulating levels of tumor derived EVs of patients have been correlated with incidence of metastasis and disease relapse.

Theranostic radiopharmaceuticals targeting cancer-associated fibroblasts

2020 ◽  
Vol 13 ◽  
Author(s):  
Fedor Zhuravlev
Keyword(s):  
Extracellular Matrix ◽  
Immune Evasion ◽  
Stromal Cells ◽  
Tumor Stroma ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Cancer Associated Fibroblasts ◽  
Malignant Cells ◽  
Anti Cancer ◽  
Tumor Growth And Metastasis

The tumor microenvironment is a dynamic ecosystem where malignant cells interact with the stromal cells sustaining and promoting tumor growth and metastasis. Cancer-associated fibroblasts (CAFs) are the major component of tumor stroma. CAFs control key tumorigenic activities by participating in immune evasion and suppression, extracellular matrix remodeling, neo-angiogenesis, and drug resistance. Therefore, targeting CAFs emerges as an attractive anti-cancer strategy. This review summarized recent advancements in targeting CAFs with diagnostic and therapeutic radiopharmaceuticals using clinically-promising biomarkers. The efforts to improve clinical outcomes via application of new radiotheranostic compounds are discussed in the context of radionuclide, the pharmacophore, and, more generally, in terms of biomarker specificity and expression across different cancers and CAF phenotypes.

Mystery of tumor specific immunity: LIGHT turns on silent tumor specific immunity

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20107-20107
Author(s):  
L. T. Cao
Keyword(s):  
T Cells ◽  
Immune System ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Tumor Antigens ◽  
Virus Entry ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Specific Immunity ◽  
Herpès Virus

20107 Background: More than 2000 tumor antigens have been identified so far. However, none of these tumor antigens are approved to be immunogenic. Genetic alteration which activates uncontrolled cell growth transforms normal cells to tumor cells. Tumor cells, therefore, do not carry any foreign antigens and thus tumor antigens are not immunogenic (unless in the presence of viral infection). The so-called tumor specific immunity is actually the host versus graft effect, not specific for tumors. Methods and Results: Using proper controlled tissue graft as control, our previous data indicated that the hosts could accept both the graft and the tumor. The immune system is silent to tumor antigens. By transfecting tumor cells with a modified LIGHT (Lymphotoxins, shows Inducible expression, and completes with herpes simplex virus Glycoprotein D for Herpes virus entry mediator, a receptor expressed by T lymphocytes) expressing vectors, Dr. Fu at the University of Chicago is able to eradicate tumors in his animal model. The expressed LIGHT on the tumor cell surface serves as tether for the naïve T cells and the stromal cells by binding to lymphotoxin-beta receptor on stromal cells and herpes virus entry mediator on T cells. The trio of tumor-LIGHT-stroma working like a foreign antigen attracts naïve T cells and increases the infiltration of naïve T cells within the tumors. The trio then co-activates naïve T cells to destroy tumors. The LIGHT mechanism may be similar to that in autoimmune phenomenon. Conclusion: Tumor specific immunity may be silent; however we can modify tumor antigens and activate silent immune system to destroy tumors. We currently have four immunotherapies against cancer. The LIGHT approach or in situ co-stimulation therapy, vaccine therapy, and ex vivo cell-transfer therapy are three active immunotherapies. The fourth one is a passive immunotherapy: the near-specific, personalized immunotherapy. No significant financial relationships to disclose.

scholarly journals The Extracellular Matrix Environment of Clear Cell Renal Cell Carcinoma Determines Cancer Associated Fibroblast Growth

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5873
Author(s):  
Kyle H. Bond ◽  
Takuto Chiba ◽  
Kieran P. H. Wynne ◽  
Calvin P. H. Vary ◽  
Sunder Sims-Lucas ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Extracellular Matrix ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Primary Cultures ◽  
Kidney Cortex ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and is often caused by mutations in the oxygen-sensing machinery of kidney epithelial cells. Due to its pseudo-hypoxic state, ccRCC recruits extensive vasculature and other stromal components. Conventional cell culture methods provide poor representation of stromal cell types in primary cultures of ccRCC, and we hypothesized that mimicking the extracellular environment of the tumor would promote growth of both tumor and stromal cells. We employed proteomics to identify the components of ccRCC extracellular matrix (ECM) and found that in contrast to healthy kidney cortex, laminin, collagen IV, and entactin/nidogen are minor contributors. Instead, the ccRCC ECM is composed largely of collagen VI, fibronectin, and tenascin C. Analysis of single cell expression data indicates that cancer-associated fibroblasts are a major source of tumor ECM production. Tumor cells as well as stromal cells bind efficiently to a nine-component ECM blend characteristic of ccRCC. Primary patient-derived tumor cells bind the nine-component blend efficiently, allowing to us to establish mixed primary cultures of tumor cells and stromal cells. These miniature patient-specific replicas are conducive to microscopy and can be used to analyze interactions between cells in a model tumor microenvironment.

Dysregulation of synovial fibroblasts in rheumatoid arthritis

2020 ◽  
pp. 55-64
Author(s):  
Thomas Crowley ◽  
Jason D. Turner ◽  
Andrew Filer ◽  
Andy Clark ◽  
Chris Buckley
Keyword(s):  
Rheumatoid Arthritis ◽  
Extracellular Matrix ◽  
Immune System ◽  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Stromal Cells ◽  
Synovial Fibroblasts ◽  
Traditional Role ◽  
Level Of Involvement

Fibroblasts are ubiquitous stromal cells, with populations found in all organs. The traditional role of fibroblasts was thought to be mainly structural; making and modifying extracellular matrix. Taken together the ability of fibroblasts to produce and respond to many factors involved in the immune system indicates the degree to which they are involved in orchestrating the inflammatory response in rheumatoid arthritis (RA). This level of involvement demonstrates the importance of fibroblasts in inflammation and indicates the shift from transient to chronic inflammation in RA could be facilitated in part by synovial fibroblasts. This chapter explores the role of fibroblasts in RA.

Modulation of Immuno-biome during Radio-sensitization of Tumors by Glycolytic Inhibitors

2020 ◽  
Vol 27 (24) ◽  
pp. 4002-4015 ◽  
Author(s):  
Seema Gupta ◽  
Bilikere S. Dwarakanath
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Aerobic Glycolysis ◽  
Immune Competence ◽  
Immune Stimulation ◽  
Direct Effects ◽  
Contributing Factors ◽  
Lactate Transport

The Tumor Microenvironment (TME) comprising stromal cells, fibroblasts and various components of the immune system forms a pro-tumorigenic cocoon around the tumor cells with the reprogramming of the metabolism in the form of Warburg phenotype (enhanced aerobic glycolysis) in tumor as well as non-tumor cells. This reprogramming plays a significant role in suppressing the immune response leading to the survival and proliferation of tumor cells and resistance to therapies. Therefore, there is a considerable interest in developing strategies involving metabolic modifiers to improve the therapeutic efficacy that restores immune competence, besides enhancing the direct effects on tumor cells. Inhibitors of glycolysis like 2-deoxy-D-glucose (2-DG; a hexokinase inhibitor), dichloroacetate and small molecule inhibitors of lactate transport (MCT-1) are some of the metabolic modifiers investigated for their therapeutic as well as adjuvant potential. Among these, 2-DG has been widely investigated and established as an ideal adjuvant in the radio- and chemotherapy of tumors. Modulation of the immuno-biome in the form of cytokine shifts, differential transcriptional regulation, abrogation of immunosuppressive network and reduced accumulation of lactate are some of the contributing factors for immune stimulation linked to the radio- and chemosensitization by glycolytic inhibitors.

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 The crosstalk between circular RNAs and the tumor microenvironment in cancer metastasis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ying Shao ◽  
Bingjian Lu
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Blood Vessels ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Cancer Metastasis ◽  
Circular Rnas ◽  
Anoikis Resistance ◽  
Non Coding Rnas

Abstract Background Carcinomas are highly heterogeneous with regard to various cancer cells within a tumor microenvironment (TME), which is composed of stromal cells, blood vessels, immunocytes, and modified extracellular matrix. Focus of the study Circular RNAs (circRNAs) are non-coding RNAs that are expressed in cancer and stromal cells. They are closely associated with cancer metastasis as their expression in tumor cells directs the latter to migrate to different organs. circRNAs packaged in exosomes might be involved in this process. This is particularly important as the TME acts in tandem with cancer cells to enhance their proliferation and metastatic capability. In this review, we focus on recent studies on the crosstalk between circRNAs and the TME during cancer metastasis. Conclusion We particularly emphasize the roles of the interaction between circRNAs and the TME in anoikis resistance, vessel co-option, and local circRNA expression in directing homing of exosome.

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