scholarly journals MicroRNA-Mediated Metabolic Shaping of the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 127
Author(s):  
Federico Virga ◽  
Lorena Quirico ◽  
Stefania Cucinelli ◽  
Massimiliano Mazzone ◽  
Daniela Taverna ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Immune Cells ◽  
Metabolic Reprogramming ◽  
Stromal Fibroblasts ◽  
Metabolic Alterations ◽  
Cell Functions ◽  
Cancer Management ◽  
Mrna Targets

The metabolism of cancer cells is generally very different from what is found in normal counterparts. However, in a tumor mass, the continuous crosstalk and competition for nutrients and oxygen among different cells lead to metabolic alterations, not only in cancer cells, but also in the different stromal and immune cells of the tumor microenvironment (TME), which are highly relevant for tumor progression. MicroRNAs (miRs) are small non-coding RNAs that silence their mRNA targets post-transcriptionally and are involved in numerous physiological cell functions as well as in the adaptation to stress situations. Importantly, miRs can also be released via extracellular vesicles (EVs) and, consequently, take part in the bidirectional communication between tumor and surrounding cells under stress conditions. Certain miRs are abundantly expressed in stromal and immune cells where they can regulate various metabolic pathways by directly suppressing enzymes or transporters as well as by controlling important regulators (such as transcription factors) of metabolic processes. In this review, we discuss how miRs can induce metabolic reprogramming in stromal (fibroblasts and adipocytes) and immune (macrophages and T cells) cells and, in turn, how the biology of the different cells present in the TME is able to change. Finally, we debate the rebound of miR-dependent metabolic alterations on tumor progression and their implications for cancer management.

The Engaged Role of Tumor Microenvironment in Cancer Metabolism: Focusing on Cancer-Associated Fibroblast and Exosome Mediators

2020 ◽  
Vol 21 (2) ◽  
pp. 254-266 ◽  
Author(s):  
Khandan Ilkhani ◽  
Milad Bastami ◽  
Soheila Delgir ◽  
Asma Safi ◽  
Shahrzad Talebian ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Krebs Cycle ◽  
Metabolic Reprogramming ◽  
Cancer Management ◽  
Cancer Associated Fibroblast ◽  
Potential Biomarker ◽  
Close Relationship ◽  
Microenvironmental Factors

: Metabolic reprogramming is a significant property of various cancer cells, which most commonly arises from the Tumor Microenvironment (TME). The events of metabolic pathways include the Warburg effect, shifting in Krebs cycle metabolites, and the rate of oxidative phosphorylation, potentially providing energy and structural requirements for the development and invasiveness of cancer cells. TME and tumor metabolism shifting have a close relationship through bidirectional signaling pathways between stromal and tumor cells. Cancer- Associated Fibroblasts (CAFs), as the most dominant cells of TME, play a crucial role in the aberrant metabolism of cancer. Furthermore, the stated relationship can affect survival, progression, and metastasis in cancer development. Recently, exosomes are considered one of the most prominent factors in cellular communications considering effective content and bidirectional mediatory effect between tumor and stromal cells. In this regard, CAF-Derived Exosomes (CDE) exhibit an efficient obligation to induce metabolic reprogramming for promoting growth and metastasis of cancer cells. The understanding of cancer metabolism, including factors related to TME, could lead to the discovery of a potential biomarker for diagnostic and therapeutic approaches in cancer management. This review focuses on the association between metabolic reprogramming and engaged microenvironmental, factors such as CAFs, and the associated derived exosomes.

scholarly journals Tumor-Associated Neutrophils and Macrophages—Heterogenous but Not Chaotic

2020 ◽  
Vol 11 ◽  
Author(s):  
Ling Wu ◽  
Xiang H.-F. Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Immune Cells ◽  
Mutual Influence ◽  
Therapeutic Resistance ◽  
Tumor Associated Macrophages ◽  
Tumor Associated Neutrophils ◽  
Shed Light ◽  
Lines Of Evidence

Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) have been extensively studied. Their pleotropic roles were observed in multiple steps of tumor progression and metastasis, and sometimes appeared to be inconsistent across different studies. In this review, we collectively discussed many lines of evidence supporting the mutual influence between cancer cells and TAMs/TANs. We focused on how direct interactions among these cells dictate co-evolution involving not only clonal competition of cancer cells, but also landscape shift of the entire tumor microenvironment (TME). This co-evolution may take distinct paths and contribute to the heterogeneity of cancer cells and immune cells across different tumors. A more in-depth understanding of the cancer-TAM/TAN co-evolution will shed light on the development of TME that mediates metastasis and therapeutic resistance.

scholarly journals Metabolic Alterations in Pancreatic Cancer Progression

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 2 ◽  
Author(s):  
Enza Vernucci ◽  
Jaime Abrego ◽  
Venugopal Gunda ◽  
Surendra K. Shukla ◽  
Aneesha Dasgupta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Precancerous Lesions ◽  
Genetically Engineered ◽  
Metabolic Reprogramming ◽  
Pancreatic Tumors ◽  
Metabolic Alterations ◽  
Genetically Engineered Mice

Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic cells only, we compared the metabolic profile of KPC and orthotopic tumors with those obtained from KPC-tumor derived cell lines. We observed significant upregulation of glycolysis and the pentose phosphate pathway metabolites even at the early stages of pathogenesis. Other biosynthetic pathways also demonstrated a few common perturbations. While some of the metabolic changes in tumor cells are not detectable in orthotopic and spontaneous tumors, a significant number of tumor cell-intrinsic metabolic alterations are readily detectable in the animal models. Overall, we identified that metabolic alterations in precancerous lesions are maintained during cancer development and are largely mirrored by cancer cells in culture conditions.

scholarly journals The Immune Endocannabinoid System of the Tumor Microenvironment

2020 ◽  
Vol 21 (23) ◽  
pp. 8929
Author(s):  
Melanie Kienzl ◽  
Julia Kargl ◽  
Rudolf Schicho
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Immune Cells ◽  
Cannabinoid Receptors ◽  
Immune Cell ◽  
Tumor Development ◽  
Endocannabinoid System ◽  
Cell Functions ◽  
In Vitro Effects

Leukocytes are part of the tumor microenvironment (TME) and are critical determinants of tumor progression. Because of the immunoregulatory properties of cannabinoids, the endocannabinoid system (ECS) may have an important role in shaping the TME. Members of the ECS, an entity that consists of cannabinoid receptors, endocannabinoids and their synthesizing/degrading enzymes, have been associated with both tumor growth and rejection. Immune cells express cannabinoid receptors and produce endocannabinoids, thereby forming an “immune endocannabinoid system”. Although in vitro effects of exogenous cannabinoids on immune cells are well described, the role of the ECS in the TME, and hence in tumor development and immunotherapy, is still elusive. This review/opinion discusses the possibility that the “immune endocannabinoid system” can fundamentally influence tumor progression. The widespread influence of cannabinoids on immune cell functions makes the members of the ECS an interesting target that could support immunotherapy.

scholarly journals Metabolites in the Tumor Microenvironment Reprogram Functions of Immune Effector Cells Through Epigenetic Modifications

2021 ◽  
Vol 12 ◽  
Author(s):  
Yijia Li ◽  
Yangzhe Wu ◽  
Yi Hu
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Immune Cells ◽  
Expression Patterns ◽  
Immune Effector ◽  
Effector Cells ◽  
Cell Functions ◽  
Metabolic Plasticity ◽  
Signal Transduction Networks ◽  
Immune Effector Cells

Cellular metabolism of both cancer and immune cells in the acidic, hypoxic, and nutrient-depleted tumor microenvironment (TME) has attracted increasing attention in recent years. Accumulating evidence has shown that cancer cells in TME could outcompete immune cells for nutrients and at the same time, producing inhibitory products that suppress immune effector cell functions. Recent progress revealed that metabolites in the TME could dysregulate gene expression patterns in the differentiation, proliferation, and activation of immune effector cells by interfering with the epigenetic programs and signal transduction networks. Nevertheless, encouraging studies indicated that metabolic plasticity and heterogeneity between cancer and immune effector cells could provide us the opportunity to discover and target the metabolic vulnerabilities of cancer cells while potentiating the anti-tumor functions of immune effector cells. In this review, we will discuss the metabolic impacts on the immune effector cells in TME and explore the therapeutic opportunities for metabolically enhanced immunotherapy.

scholarly journals Cancer: An Oxidative Crosstalk between Solid Tumor Cells and Cancer Associated Fibroblasts

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Alessandro Arcucci ◽  
Maria Rosaria Ruocco ◽  
Giuseppina Granato ◽  
Anna Maria Sacco ◽  
Stefania Montagnani
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Critical Role ◽  
Metabolic Reprogramming ◽  
Antioxidant Systems ◽  
Activation Process ◽  
Cancer Associated Fibroblasts

Redox balance is associated with the regulation of several cell signalling pathways and functions. In fact, under physiological conditions, cells maintain a balance between oxidant and antioxidant systems, and reactive oxygen species (ROS) can act as second messengers to regulate cell proliferation, cell death, and other physiological processes. Cancer tissues usually contain higher levels of ROS than normal tissues, and this ROS overproduction is associated with tumor development. Neoplastic tissues are very heterogeneous systems, composed of tumor cells and microenvironment that has a critical role in tumor progression. Cancer associated fibroblasts (CAFs) represent the main cell type of tumor microenvironment, and they contribute to tumor growth by undergoing an irreversible activation process. It is known that ROS can be transferred from cancer cells to fibroblasts. In particular, ROS affect the behaviour of CAFs by promoting the conversion of fibroblasts to myofibroblasts that support tumor progression and dissemination. Furthermore, the wrecking of redox homeostasis in cancer cells and tumor microenvironment induces a metabolic reprogramming in tumor cells and cancer associated fibroblasts, giving advantage to cancer growth. This review describes the role of ROS in tumor growth, by focusing on CAFs activation and metabolic interactions between cancer cells and stromal fibroblasts.

scholarly journals The Janus Face of Tumor Microenvironment Targeted by Immunotherapy

2019 ◽  
Vol 20 (17) ◽  
pp. 4320 ◽  
Author(s):  
Buoncervello ◽  
Gabriele ◽  
Toschi
Keyword(s):  
Tumor Microenvironment ◽  
T Lymphocytes ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Immune Cells ◽  
Antitumor Immunity ◽  
Therapeutic Response ◽  
Tumor Development ◽  
Response To Therapy ◽  
Cd8 T Lymphocytes

The tumor microenvironment (TME) is a complex entity where host immune and non-immune cells establish a dynamic crosstalk with cancer cells. Through cell-cell interactions, which are mediated by key signals, such as the PD-1/PD-L1 axis, as well as the release of soluble mediators, this articulated process defines the nature of TME determining tumor development, prognosis, and response to therapy. Specifically, tumors are characterized by cellular plasticity that allows for the microenvironment to polarize towards inflammation or immunosuppression. Thus, the dynamic crosstalk among cancer, stromal, and immune components crucially favors the dominance of one of the Janus-faced contexture of TME crucial to the outcome of tumor development and therapeutic response. However, mostly, TME is dominated by an immunosuppressive landscape that blocks antitumor immunity and sustain tumor progression. Hence, in most cases, the immunosuppressive components of TME are highly competent in suppressing tumor-specific CD8+ T lymphocytes, the effectors of cancer destruction. In this complex context, immunotherapy aims to arm the hidden Janus face of TME disclosing and potentiating antitumor immune signals. Herein, we discuss recent knowledge on the immunosuppressive crosstalk within TME, and share perspectives on how immunotherapeutic approaches may exploit tumor immune signals to generate antitumor immunity.

scholarly journals Genome Scale Modeling to Study the Metabolic Competition between Cells in the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4609
Author(s):  
Itziar Frades ◽  
Carles Foguet ◽  
Marta Cascante ◽  
Marcos J. Araúzo-Bravo
Keyword(s):  
Steady State ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Immune Cells ◽  
Building Blocks ◽  
Linear Constraints ◽  
Metabolic Reprogramming ◽  
Tissue Specific ◽  
Metabolic Fluxes ◽  
Genome Scale

The tumor’s physiology emerges from the dynamic interplay of numerous cell types, such as cancer cells, immune cells and stromal cells, within the tumor microenvironment. Immune and cancer cells compete for nutrients within the tumor microenvironment, leading to a metabolic battle between these cell populations. Tumor cells can reprogram their metabolism to meet the high demand of building blocks and ATP for proliferation, and to gain an advantage over the action of immune cells. The study of the metabolic reprogramming mechanisms underlying cancer requires the quantification of metabolic fluxes which can be estimated at the genome-scale with constraint-based or kinetic modeling. Constraint-based models use a set of linear constraints to simulate steady-state metabolic fluxes, whereas kinetic models can simulate both the transient behavior and steady-state values of cellular fluxes and concentrations. The integration of cell- or tissue-specific data enables the construction of context-specific models that reflect cell-type- or tissue-specific metabolic properties. While the available modeling frameworks enable limited modeling of the metabolic crosstalk between tumor and immune cells in the tumor stroma, future developments will likely involve new hybrid kinetic/stoichiometric formulations.

scholarly journals Current Trends in Non-Invasive Imaging of Interactions in the Liver Tumor Microenvironment Mediated by Tumor Metabolism

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3645
Author(s):  
Isabel Theresa Schobert ◽  
Lynn Jeanette Savic
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Imaging Techniques ◽  
Treatment Strategies ◽  
Tumor Metabolism ◽  
Resistance Mechanisms ◽  
Metabolic Reprogramming ◽  
Non Invasive

With the increasing understanding of resistance mechanisms mediated by the metabolic reprogramming in cancer cells, there is a growing clinical interest in imaging technologies that allow for the non-invasive characterization of tumor metabolism and the interactions of cancer cells with the tumor microenvironment (TME) mediated through tumor metabolism. Specifically, tumor glycolysis and subsequent tissue acidosis in the realms of the Warburg effect may promote an immunosuppressive TME, causing a substantial barrier to the clinical efficacy of numerous immuno-oncologic treatments. Thus, imaging the varying individual compositions of the TME may provide a more accurate characterization of the individual tumor. This approach can help to identify the most suitable therapy for each individual patient and design new targeted treatment strategies that disable resistance mechanisms in liver cancer. This review article focuses on non-invasive positron-emission tomography (PET)- and MR-based imaging techniques that aim to visualize the crosstalk between tumor cells and their microenvironment in liver cancer mediated by tumor metabolism.

Sign in / Sign up

Export Citation Format

Share Document