scholarly journals The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Drenka Trivanović ◽  
Jelena Krstić ◽  
Ivana Okić Djordjević ◽  
Slavko Mojsilović ◽  
Juan Francisco Santibanez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Tumor Microenvironment ◽  
Tumor Tissue ◽  
Tumor Development ◽  
Antitumor Therapy ◽  
Delivery Vehicles ◽  
Stromal Stem Cells ◽  
Immunomodulatory Potential ◽  
Functional Phenotype

State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.

Shared and Divergent Stimulatory Effects of S100A4 and Uric Acid on Proliferation and Chemotaxis of Mesenchymal Stem Cells (MSCs). Interplay Between Necrotic Tumor Material and Immunosuppressive MSCs within Tumor Microenvironment,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3239-3239
Author(s):  
Judith Luiza Eisenbacher ◽  
Tatjana Yildiz ◽  
Hubert Schrezenmeier ◽  
Ramin Lotfi
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Mesenchymal Stem Cells ◽  
Uric Acid ◽  
Tumor Microenvironment ◽  
Tumor Tissue ◽  
Chemotactic Activity ◽  
Necrotic Tumor ◽  
Tumor Material ◽  
Dose Dependent

Abstract Abstract 3239 Background: Necrotic cell death is a characteristic feature of advanced solid tumor. S100 proteins and uric acid (UA) are released from necrotic (tumor) tissue regardless of tumor's origin. Both of these factors are known to influence immune response. Mesenchymal stem cells (MSCs) are often found within tumor microenvironment and are associated with poor prognosis of cancer patients in terms of metastasis and survival. MSCs seem to play a crucial role within tumor microenvironment probably due to their immunosuppressive capacity interfering with the specific anti-tumor immune response. Underlying mechanisms for MSC accumulation and stimulation in tumor tissue are not well characterized yet. S100A4 is known to promote metastasis in certain tumors such as colorectal cancer, but the exact mechanism of this effect still remains unclear. UA not only induces an acute inflammatory response but is also known to maintain chronic inflammation. In our previous experiments, we could already show that necrotic tumor material is capable of inducing chemotaxis and proliferation of MSCs. Focusing on S100A4 and UA, we now sought to characterize individual known factors within necrotic material which may be responsible for described effects. Materials and Methods: Proliferation assays were performed using CYQUANT Assay (Invitrogen) based on fluorescent staining of nucleic acid. Migration of fluorescent-labeled MSCs was assessed using FluoroBlok (BD) two-chamber chemotaxis plates, fluorescence within the bottom chamber of migration plates was measured with PolarStar plate reader (BMG). Results: We tested the influence of recombinant human S100A4 at concentrations between 50 and 1000 ng/ml on MSC proliferation and could demonstrate divergent effects depending on the chosen S100A4 concentration: S100A4 at concentrations not higher than 100 ng/ml enhanced the proliferation of MSCs in a dose dependent manner up to 50%, whereas concentrations above 100 ng/ml inhibited MSC proliferation down to 50% compared to medium containing 5% human serum without S100A4. We tested the chemotactic activity of recombinant human S100A4 at concentrations between 0.01 and 1000 ng/ml on MSCs and could demonstrate a dose dependent chemotactic activity up to 80% of the response which was achieved by positive control (50% FBS). By adding UA to suboptimal concentration of S100A4 (100ng/ml), we could enhance the chemotactic activity of S100A4 on MSCs. In contrast to its enhancing effect on MSC migration, UA inhibited dose dependently the proliferation inducing effect of S100A4 with strongest effect at 300μg UA/ml resulting in about 50% inhibition of proliferation compared to medium containing 100ng/ml S100A4 without additional UA. ELISA assays confirmed the presence of S100A4 in the necrotic tumor material which we had used in our previous experiments with similar stimulatory effects on MSCs in terms of proliferation and chemotaxis. Conclusions: MSCs are often found within tumor tissue and may influence the biologic behavior of tumor and host's immune response to tumor. We could characterize UA and S100A4 as bioactive factors within necrotic (tumor) material. Whereas S100A4 stimulated both proliferation as well as chemotaxis of MSCs, UA enhanced the chemotactic acitivity of S100A4 while inhibiting its proliferation inducing effect. Comparing our new data with our previous observations using tumor lysates to induce chemotaxis and proliferation of MSCs the overall effect of necrotic material seems to be rather proliferative and chemotactic even though some factors like UA may interfere with mentioned overall effects. Keeping in mind that MSCs can act as potent immunosuppressive cells, we conclude that tumor necrosis rather inhibits an effective anti-tumor immune response by favoring accumulation and proliferation of MSCs within tumor microenvironment. Our observations shed some light into the biology of MSCs within tumor microenvironment and open new questions concerning the interplay between MSCs, necrotic tumor cells and tumor progression. Possible strategies to break the described vicious circle by rather inducing an apoptotic tumor cell death or by reducing bioactive factors released from necrotic tissue within tumor microenvironment may be considered. Additionally, clinical investigations using specific antibodies to S100A4 or influencing serum concentrations of UA in tumor patients may be performed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Latest Advances in Targeting the Tumor Microenvironment for Tumor Suppression

2019 ◽  
Vol 20 (19) ◽  
pp. 4719 ◽  
Author(s):  
Chloé Laplagne ◽  
Marcin Domagala ◽  
Augustin Le Naour ◽  
Christophe Quemerais ◽  
Dimitri Hamel ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Small Molecules ◽  
Tumor Development ◽  
Cell Types ◽  
Host Cells ◽  
Matrix Proteins ◽  
Cancer Cell Survival ◽  
Cancer Setting ◽  
Interfering Rna ◽  
Stromal Stem Cells

The tumor bulk is composed of a highly heterogeneous population of cancer cells, as well as a large variety of resident and infiltrating host cells, extracellular matrix proteins, and secreted proteins, collectively known as the tumor microenvironment (TME). The TME is essential for driving tumor development by promoting cancer cell survival, migration, metastasis, chemoresistance, and the ability to evade the immune system responses. Therapeutically targeting tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), regulatory T-cells (T-regs), and mesenchymal stromal/stem cells (MSCs) is likely to have an impact in cancer treatment. In this review, we focus on describing the normal physiological functions of each of these cell types and their behavior in the cancer setting. Relying on the specific surface markers and secreted molecules in this context, we review the potential targeting of these cells inducing their depletion, reprogramming, or differentiation, or inhibiting their pro-tumor functions or recruitment. Different approaches were developed for this targeting, namely, immunotherapies, vaccines, small interfering RNA, or small molecules.

Increased Arginase1 expression in tumor microenvironment promotes mammary carcinogenesis via multiple mechanisms

2020 ◽  
Author(s):  
Michela Croce ◽  
Patrizia Damonte ◽  
Monica Morini ◽  
Simona Pigozzi ◽  
Laura Chiossone ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Mammary Tumor ◽  
Cell Function ◽  
Tumor Development ◽  
Mammary Carcinogenesis ◽  
Mouse Line ◽  
Arginine Metabolism ◽  
Transgenic Mouse Line

Abstract Arginine metabolism plays a significant role in regulating cell function, affecting tumor growth and metastatization. To study the effect of the arginine-catabolizing enzyme Arginase1 (ARG1) on tumor microenvironment, we generated a mouse model of mammary carcinogenesis by crossbreeding a transgenic mouse line overexpressing ARG1 in macrophages (FVBArg+/+) with the MMTV-Neu mouse line (FVBNeu+/+). This double transgenic line (FVBArg+/−;Neu+/+) showed a significant shortening in mammary tumor latency, and an increase in the number of mammary nodules. Transfer of tumor cells from FVBNeu+/+ into either FVB wild type or FVBArg+/+ mice resulted in increase regulatory T cells in the tumor infiltrate, suggestive of an impaired antitumor immune response. However, we also found increased frequency of tumor stem cells in tumors from FVBArg+/−;Neu+/+ transgenic compared with FVBNeu+/+ mice, suggesting that increased arginine metabolism in mammary tumor microenvironment may supports the cancer stem cells niche. We provide in vivo evidence of a novel, yet unexploited, mechanism through which ARG1 may contribute to tumor development.

scholarly journals The Interaction Between the Microbiome and Tumors

2021 ◽  
Vol 11 ◽  
Author(s):  
Yawen Zong ◽  
Yujie Zhou ◽  
Binyou Liao ◽  
Min Liao ◽  
Yangyang Shi ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Tissue ◽  
Tumor Development ◽  
Healthy Individuals ◽  
Tumor Tissues ◽  
Incidence And Mortality ◽  
Consistent Increase ◽  
Novel Therapeutic Strategies ◽  
Pathogenic Process ◽  
Global Health Problem

Cancer is a significant global health problem and is characterized by a consistent increase in incidence and mortality rate. Deciphering the etiology and risk factors are essential parts of cancer research. Recently, the altered microbiome has been identified within the tumor microenvironment, tumor tissue, and even nonadjacent environments, which indicates a strong correlation between the microbiome and tumor development. However, the causation and mechanisms of this correlation remain unclear. Herein, we summarized and discussed the interaction between the microbiome and tumor progression. Firstly, the microbiome, which can be located in the tumor microenvironment, inside tumor tissues and in the nonadjacent environment, is different between cancer patients and healthy individuals. Secondly, the tumor can remodel microbial profiles by creating a more beneficial condition for the shifted microbiome. Third, the microbiome can promote tumorigenesis through a direct pathogenic process, including the establishment of an inflammatory environment and its effect on host immunity. The interactions between the microbiome and tumors can promote an understanding of the carcinogenesis and provide novel therapeutic strategies for cancers.

scholarly journals Mesenchymal stem cells and cancer therapy: insights into targeting the tumour vasculature

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Surendar Aravindhan ◽  
Sura Salman Ejam ◽  
Methaq Hadi Lafta ◽  
Alexander Markov ◽  
Alexei Valerievich Yumashev ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Tumor Tissue ◽  
Angiogenic Therapy ◽  
Final Destination ◽  
Tumour Vasculature

AbstractA crosstalk established between tumor microenvironment and tumor cells leads to contribution or inhibition of tumor progression. Mesenchymal stem cells (MSCs) are critical cells that fundamentally participate in modulation of the tumor microenvironment, and have been reported to be able to regulate and determine the final destination of tumor cell. Conflicting functions have been attributed to the activity of MSCs in the tumor microenvironment; they can confer a tumorigenic or anti-tumor potential to the tumor cells. Nonetheless, MSCs have been associated with a potential to modulate the tumor microenvironment in favouring the suppression of cancer cells, and promising results have been reported from the preclinical as well as clinical studies. Among the favourable behaviours of MSCs, are releasing mediators (like exosomes) and their natural migrative potential to tumor sites, allowing efficient drug delivering and, thereby, efficient targeting of migrating tumor cells. Additionally, angiogenesis of tumor tissue has been characterized as a key feature of tumors for growth and metastasis. Upon introduction of first anti-angiogenic therapy by a monoclonal antibody, attentions have been drawn toward manipulation of angiogenesis as an attractive strategy for cancer therapy. After that, a wide effort has been put on improving the approaches for cancer therapy through interfering with tumor angiogenesis. In this article, we attempted to have an overview on recent findings with respect to promising potential of MSCs in cancer therapy and had emphasis on the implementing MSCs to improve them against the suppression of angiogenesis in tumor tissue, hence, impeding the tumor progression.

scholarly journals TRAIL delivered by mesenchymal stromal/stem cells counteracts tumor development in orthotopic Ewing sarcoma models

2016 ◽  
Vol 139 (12) ◽  
pp. 2802-2811 ◽  
Author(s):  
Romain Guiho ◽  
Kevin Biteau ◽  
Giulia Grisendi ◽  
Julien Taurelle ◽  
Mathias Chatelais ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ewing Sarcoma ◽  
Tumor Development ◽  
Stromal Stem Cells

scholarly journals One cell, multiple roles: contribution of mesenchymal stem cells to tumor development in tumor microenvironment

2013 ◽  
Vol 3 (1) ◽  
pp. 5 ◽  
Author(s):  
Xue Yang ◽  
Jing Hou ◽  
Zhipeng Han ◽  
Ying Wang ◽  
Chong Hao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Tumor Development ◽  
Multiple Roles

scholarly journals Single‐cell high‐content imaging parameters predict functional phenotype of cultured human bone marrow stromal stem cells

2019 ◽  
Vol 9 (2) ◽  
pp. 189-202 ◽  
Author(s):  
Justyna M. Kowal ◽  
Hagen Schmal ◽  
Ulrich Halekoh ◽  
Jacob B. Hjelmborg ◽  
Moustapha Kassem
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Single Cell ◽  
Human Bone ◽  
Human Bone Marrow ◽  
High Content Imaging ◽  
Imaging Parameters ◽  
Stromal Stem Cells ◽  
Functional Phenotype

scholarly journals Revisiting Cancer Stem Cells as the Origin of Cancer-Associated Cells in the Tumor Microenvironment: A Hypothetical View from the Potential of iPSCs

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 879 ◽  
Author(s):  
Amira Osman ◽  
Said M. Afify ◽  
Ghmkin Hassan ◽  
Xiaoying Fu ◽  
Akimasa Seno ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Stromal Cells ◽  
Tumor Development ◽  
Normal Tissues ◽  
Lineage Differentiation ◽  
Tumor Growth And Metastasis ◽  
Induced Pluripotent

The tumor microenvironment (TME) has an essential role in tumor initiation and development. Tumor cells are considered to actively create their microenvironment during tumorigenesis and tumor development. The TME contains multiple types of stromal cells, cancer-associated fibroblasts (CAFs), Tumor endothelial cells (TECs), tumor-associated adipocytes (TAAs), tumor-associated macrophages (TAMs) and others. These cells work together and with the extracellular matrix (ECM) and many other factors to coordinately contribute to tumor growth and maintenance. Although the types and functions of TME cells are well understood, the origin of these cells is still obscure. Many scientists have tried to demonstrate the origin of these cells. Some researchers postulated that TME cells originated from surrounding normal tissues, and others demonstrated that the origin is cancer cells. Recent evidence demonstrates that cancer stem cells (CSCs) have differentiation abilities to generate the original lineage cells for promoting tumor growth and metastasis. The differentiation of CSCs into tumor stromal cells provides a new dimension that explains tumor heterogeneity. Using induced pluripotent stem cells (iPSCs), our group postulates that CSCs could be one of the key sources of CAFs, TECs, TAAs, and TAMs as well as the descendants, which support the self-renewal potential of the cells and exhibit heterogeneity. In this review, we summarize TME components, their interactions within the TME and their insight into cancer therapy. Especially, we focus on the TME cells and their possible origin and also discuss the multi-lineage differentiation potentials of CSCs exploiting iPSCs to create a society of cells in cancer tissues including TME.

scholarly journals Cross Talk of Macrophages with Tumor Microenvironment Cells and Modulation of Macrophages in Cancer by Virotherapy

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1309
Author(s):  
Sarah Di Somma ◽  
Fabiana Napolitano ◽  
Giuseppe Portella ◽  
Anna Maria Malfitano
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Tumor Response ◽  
Cell Interaction ◽  
Oncolytic Viruses ◽  
Malignant Cells ◽  
Cellular Compartments ◽  
Stromal Stem Cells

Cellular compartments constituting the tumor microenvironment including immune cells, fibroblasts, endothelial cells, and mesenchymal stromal/stem cells communicate with malignant cells to orchestrate a series of signals that contribute to the evolution of the tumor microenvironment. In this study, we will focus on the interplay in tumor microenvironment between macrophages and mesenchymal stem cells and macrophages and fibroblasts. In particular, cell–cell interaction and mediators secreted by these cells will be examined to explain pro/anti-tumor phenotypes induced in macrophages. Nonetheless, in the context of virotherapy, the response of macrophages as a consequence of treatment with oncolytic viruses will be analyzed regarding their polarization status and their pro/anti-tumor response.

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