scholarly journals Different Tumor Microenvironments Lead to Different Metabolic Phenotypes

2021 ◽  
pp. 137-147
Author(s):  
Marjorie Justine Antonio ◽  
Cissy Zhang ◽  
Anne Le
Keyword(s):  
Cancer Research ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
First Century ◽  
Gene Expressions ◽  
Metabolic Phenotypes ◽  
Tumor Microenvironments ◽  
Metabolic Adaptations ◽  
New Knowledge

AbstractThe beginning of the twenty-first century offered new advances in cancer research, including new knowledge about the tumor microenvironment (TME). Because TMEs provide the niches in which cancer cells, fibroblasts, lymphocytes, and immune cells reside, they play a crucial role in cancer cell development, differentiation, survival, and proliferation. Throughout cancer progression, the TME constantly evolves, causing cancer cells to adapt to the new conditions. The heterogeneity of cancer, evidenced by diverse proliferation rates, cellular structures, metabolisms, and gene expressions, presents challenges for cancer treatment despite the advances in research. This chapter discusses how different TMEs lead to specific metabolic adaptations that drive cancer progression.

scholarly journals Blood and Cancer: Cancer Stem Cells as Origin of Hematopoietic Cells in Solid Tumor Microenvironments

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1293 ◽  
Author(s):  
Ghmkin Hassan ◽  
Masaharu Seno
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cancer Cells ◽  
Solid Tumor ◽  
Immune Cells ◽  
Hematopoietic Cells ◽  
Hematopoietic Stem ◽  
Tumor Microenvironments

The concepts of hematopoiesis and the generation of blood and immune cells from hematopoietic stem cells are some steady concepts in the field of hematology. However, the knowledge of hematopoietic cells arising from solid tumor cancer stem cells is novel. In the solid tumor microenvironment, hematopoietic cells play pivotal roles in tumor growth and progression. Recent studies have reported that solid tumor cancer cells or cancer stem cells could differentiate into hematopoietic cells. Here, we discuss efforts and research that focused on the presence of hematopoietic cells in tumor microenvironments. We also discuss hematopoiesis from solid tumor cancer stem cells and clarify the notion of differentiation of solid tumor cancer stem cells into non-cancer hematopoietic stem cells.

scholarly journals Vitamins and Cancer Immunotherapy

2022 ◽  
Vol 10 (1) ◽  
pp. 007-010
Author(s):  
Michael John Dochniak
Keyword(s):  
Cancer Research ◽  
Vitamin A ◽  
Treatment Outcomes ◽  
Cancer Cells ◽  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Cellular Growth ◽  
Complex Interplay ◽  
Improve Treatment ◽  
Growth And Nutrition

Vitamins are essential for cellular growth and nutrition. The bioavailability of vitamins may affect the immune system’s ability to fight cancer. Research efforts investigate the complex interplay of vitamins, immune cells, and cancer cells to improve treatment outcomes. This review explores managing the intake of vitamin A, B, C, D, E, and K to enhance the efficacy of forced-atopy cancer immunotherapy.

scholarly journals The force awakens: metastatic dormant cancer cells

2020 ◽  
Vol 52 (4) ◽  
pp. 569-581 ◽  
Author(s):  
So-Yeon Park ◽  
Jeong-Seok Nam
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Surveillance ◽  
Signaling Cascades ◽  
Diagnostic Systems ◽  
Cancer Proliferation ◽  
Recurrent Cancer ◽  
Cancer Dormancy ◽  
Extracellular Molecules

Abstract Recurrent cancer that spreads to distant sites is the leading cause of disease-related death among cancer patients. Cancer cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. These dormant cancer cells (DCCs) are rarely detectable with current diagnostic systems. Moreover, they can interpret homoeostatic signals from the microenvironment, thereby evading immune surveillance and chemotherapy. Eventually, DCCs can reawaken in response to signals, which are not yet fully understood, resulting in recurrence and metastasis. Therefore, understanding the biology of DCC reawakening is key to preventing metastasis. Over the last decade, a growing body of literature has revealed the mechanisms involved in cancer dormancy and reawakening. The cytotoxic activity of immune cells can cause cancer cells to enter a dormant state, and chronic inflammation can reactivate cancer proliferation at distant sites. Upon the binding of circulating DCCs to extracellular molecules, various signaling cascades are activated and reinitiate cell proliferation. In the present review, we attempt to consolidate the existing literature to provide a framework for the understanding of this crucial step in cancer progression.

scholarly journals Role of Muscarinic Acetylcholine Signaling in Gastrointestinal Cancers

Biomedicines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 58 ◽  
Author(s):  
Mitsuru Konishi ◽  
Yoku Hayakawa ◽  
Kazuhiko Koike
Keyword(s):  
Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Muscarinic Acetylcholine Receptor ◽  
Short Review ◽  
Gastrointestinal Cancers ◽  
Epithelial Stem Cells ◽  
Muscarinic Acetylcholine

In the tumor microenvironment, various stromal and immune cells accumulate and interact with cancer cells to contribute to tumor progression. Among stromal players, nerves have recently been recognized as key regulators of tumor growth. More neurotransmitters, such as catecholamines and acetylcholine (ACh), are present in tumors, as the cells that secrete neurotransmitters accumulate by the release of neurotrophic factors from cancer cells. In this short review, we focus on the role of nerve signaling in gastrointestinal (GI) cancers. Given that muscarinic acetylcholine receptor signaling seems to be a dominant regulator of GI stem cells and cancers, we review the function and mechanism of the muscarinic ACh pathway as a regulator of GI cancer progression. Accumulating evidence suggests that ACh, which is secreted from nerves and tuft cells, stimulates GI epithelial stem cells and contributes to cancer progression via muscarinic receptors.

Extracellular vesicles in cancer progression: are they part of the problem or part of the solution?

Nanomedicine ◽  
2020 ◽  
Vol 15 (26) ◽  
pp. 2625-2641
Author(s):  
Juliete Nathali Scholl ◽  
Camila Kehl Dias ◽  
Laurent Muller ◽  
Ana Maria Oliveira Battastini ◽  
Fabrício Figueiró
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Cells ◽  
Cell Function ◽  
Cytokine Release

Extracellular vesicles (EVs) are released especially by cancer cells. They modulate the tumor microenvironment by interacting with immune cells while carrying immunosuppressive or immunostimulatory molecules. In this review, we will explore some conflicting reports regarding the immunological outcomes of EVs in cancer progression, in which they might initiate an antitumor immune response or an immunosuppressive response. Concerning immunosuppression, the role of tumor-derived EVs’ in the adenosinergic system is underexplored. The enhancement of adenosine (ADO) levels in the tumor microenvironment impairs T-cell function and cytokine release. However, some tumor-derived EVs may deliver immunostimulatory factors, promoting immunogenic activity, even with ADO production. The modulatory role of ADO over the tumor progression represents a piece in an intricate microenvironment with anti and pro tumoral seesaw-like mechanisms.

scholarly journals Generalized Portrait of Cancer Metabolic Pathways Inferred from a List of Genes Overexpressed in Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Eugenia Poliakov ◽  
David Managadze ◽  
Igor B. Rogozin
Keyword(s):  
Cancer Research ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tumor Suppressors ◽  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
Central Place ◽  
Enzymatic Reactions ◽  
Kegg Pathways ◽  
Different Types

More than half a century from postulated Warburg theory of cancer cells origin, a question of changed metabolism in cancer is again taking the central place. Generalized picture of cancer metabolism was replaced by analysis of signaling and oncogenes in each type of cancer for several decades. However, now empowered with wealth of knowledge about tumor suppressors, oncogenes, and signaling pathways, reprogramming of cellular metabolism (e.g., increased glycolysis to respiration ratio in cancer cells) reemerged as an important element of cancer progression. To analyze level of expression of various proteins including metabolic enzymes across various cancers we used dbEST and Unigene data. We delineated a list of genes that are overexpressed in different types of cancer. We also grouped overexpressed enzymes into KEGG pathways and analyzed adjacent pathways to describe enzymatic reactions that take place in cancer cells and to identify major players that are abundant in cancer protein machinery. Glycolysis/gluconeogenesis and oxidative phosphorylation are the most abundant pathways although several other pathways are enriched in genes from our list. Ubiquitously overexpressed genes could be marked as nonspecific cancer-associated genes when analyzing genes that are overexpressed in certain types of cancer. Thus the list of overexpressed genes may be a useful tool for cancer research.

scholarly journals The Role of Amino Acids in the Crosstalk Between Mesenchymal Stromal Cells and Neoplastic Cells in the Hematopoietic Niche

2021 ◽  
Vol 9 ◽  
Author(s):  
Martina Chiu ◽  
Giuseppe Taurino ◽  
Massimiliano G. Bianchi ◽  
Ovidio Bussolati
Keyword(s):  
Amino Acids ◽  
Bone Marrow ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Mesenchymal Stromal Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Bone Marrow Niche ◽  
Differentiation Potential

Within the bone marrow hematopoietic cells are in close connection with mesenchymal stromal cells (MSCs), which influence the behavior and differentiation of normal or malignant lymphoid and myeloid cells. Altered cell metabolism is a hallmark of cancer, and changes in nutrient pools and fluxes are important components of the bidirectional communication between MSCs and hematological cancer cells. Among nutrients, amino acids play a significant role in cancer progression and chemo-resistance. Moreover, selected types of cancer cells are extremely greedy for glutamine, and significantly deplete the extracellular pool of the amino acid. As a consequence, this influences the behavior of MSCs in terms of either cytokine/chemokine secretion or differentiation potential. Additionally, a direct nutritional interaction exists between MSCs and immune cells. In particular, selected subpopulations of lymphocytes are dependent upon selected amino acids, such as arginine and tryptophan, for full differentiation and competence. This review describes and discusses the nutritional interactions existing in the neoplastic bone marrow niche between MSCs and other cell types, with a particular emphasis on cancer cells and immune cells. These relationships are discussed in the perspective of potential novel therapeutic strategies based on the interference on amino acid metabolism or intercellular fluxes.

scholarly journals The Role of the Innate Immune System in Cancer Dormancy and Relapse

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5621
Author(s):  
Noah M. Chernosky ◽  
Ilaria Tamagno
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Innate Immune System ◽  
Immune Escape ◽  
Disease Process ◽  
Innate Immune ◽  
Cancer Dormancy

Metastatic spread and recurrence are intimately linked to therapy failure, which remains an overarching clinical challenge for patients with cancer. Cancer cells often disseminate early in the disease process and can remain dormant for years or decades before re-emerging as metastatic disease, often after successful treatment. The interactions of dormant cancer cells and their metastatic niche, comprised of various stromal and immune cells, can determine the length of time that cancer cells remain dormant, as well as when they reactivate. New studies are defining how innate immune cells in the primary tumor may be corrupted to help facilitate many aspects of dissemination and re-emergence from a dormant state. Although the scientific literature has partially shed light on the drivers of immune escape in cancer, the specific mechanisms regulating metastasis and dormancy in the context of anti-tumor immunity are still mostly unknown. This review follows the journey of metastatic cells from dissemination to dormancy and the onset of metastatic outgrowth and recurrent tumor development, with emphasis on the role of the innate immune system. To this end, further research identifying how immune cells interact with cancer cells at each step of cancer progression will pave the way for new therapies that target the reactivation of dormant cancer cells into recurrent, metastatic cancers.

scholarly journals Carbosilane Dendrimers Loaded with siRNA Targeting Nrf2 as a Tool to Overcome Cisplatin Chemoresistance in Bladder Cancer Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 993
Author(s):  
Leanne Ambrosio ◽  
Monica Argenziano ◽  
Marie Angèle Cucci ◽  
Margherita Grattarola ◽  
Inge A.M. de Graaf ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Kidney ◽  
Attractive Alternative ◽  
Related Factor ◽  
Carbosilane Dendrimers ◽  
Gene Expressions ◽  
Bladder Cancer Cells

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as the master regulator of antioxidant and cytoprotective gene expressions. Moreover, it plays a pivotal role in cancer progression. Nrf2 mediates the adaptive response which contributes to the resistance to chemotherapeutic pro-oxidant drugs, such as cisplatin (CDDP), in various tumors, including bladder cancers. For this reason, Nrf2 could be a promising target to overcome chemoresistance. There are several known Nrf2 pharmacological inhibitors; however, most of them are not specific. The use of a specific small interfering RNA (siRNA) targeting the Nrf2 gene (siNrf2) loaded into nanovehicles is an attractive alternative, since it can increase specificity. This study aimed to evaluate the biological activity of siNrf2 loaded on guanidine-terminated carbosilane dendrimers (GCDs) in overcoming CDDP resistance in bladder cancer cells with a high level of Nrf2. Parameters such as viability, proliferation, apoptosis, migration, and oxidative stress level were taken into account. Results demonstrated that siNrf2-GCD treatment sensitized CDDP-resistant cells to CDDP treatment. Moreover, data obtained by treating the non-cancerous human kidney HK-2 cell line strongly suggest a good safety profile of the carbosilane dendrimers loaded with siNrf2. In conclusion, we suggest that siNrf2-GCD is a promising drug delivery system for gene therapy to be used in vivo; and it may represent an important tool in the therapy of CDDP-resistant cancer.

Hippo/YAP Signaling Choreographs The Tumor Immune Microenvironment to Promote Triple Negative Breast Cancer Progression Via TAZ/IL-34 Axis

2021 ◽  
Author(s):  
Zheng Wang ◽  
Fan Wang ◽  
Xin-Yuan Ding ◽  
Tian-En Li ◽  
Hao-Yu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Immune Cells ◽  
Triple Negative ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Hippo Pathway ◽  
Immune Microenvironment

Abstract Background: Growing evidence suggests that the bidirectional interactions between cancer cells and their surrounding environment namely the tumor microenvironment (TME), contributes to cancer progression, metastasis, and resistance to treatment. Intense investigation of Hippo pathway, which controls multiple central cellular function to tumorigenesis, was focused on cancer cells. However, the role of Hippo pathway in modulating tumor–stromal interactions in triple negative breast cancer remains largely unknow. This study therefore focused on revealing effects of Hippo-YAP/TAZ signaling to immune microenvironment.Methods: The correlation between Hippo/YAP signaling and the abundance of immune cells were estimated by Immune Cell Abundance Identifier. Clinical TNBC samples from 120 patients were analyzed to assess the correlation between TAZ expression and disease prognosis as well as tumor-infiltrating immune cells. Inflammatory immune profiles, bioinformatics analysis and chromatin immunoprecipitation were performed to identify the expression of immune-related genes that were regulated by TAZ. An in vitro co-culture system was applied to investigate the crosstalk between TNBC cells and tumor-associated macrophages (TAMs) modulated by the TAZ/interleukin 34 (IL-34) axis. In vivo tumor growth and metastasis models were used to evaluate the pro-tumor functions of TAZ, IL-34, and TAMs as well as the antitumor efficacy of anti-PD-L1 and IL-34/colony-stimulating factor 1 receptor (CSF-1R) blockade.Results: In TNBC patients, high activity of Hippo pathway was correlated with decreased number of T cells, upregulated TAM infiltration, and poor prognosis. TAZ could directly regulate IL-34 and PD-L1 expression and promote IL-34 secretion in TNBC cells, leading to increased TAM infiltration and distant metastasis. TAM-derived transforming growth factor beta 1 (TGF-β1) could also induce TAZ expression in TNBC cells, thus forming a positive feedback loop between TNBC cells and TAMs. Furthermore, targeting the TAZ/IL-34 axis through its CSF-1R inhibitor could dramatically decrease TAM infiltration and significantly improve anti-PD-L1 efficacy in inhibiting metastasis in TNBC.Conclusions: Activity of Hippo pathway was associated with worse disease outcomes in TNBC and could increase TAM infiltration through the TAZ/IL-34 axis, leading to an immunosuppressive microenvironment and impairing the treatment efficacy of anti-PD-L1. Thus, the TAZ/IL-34 axis can serve as a novel target for TNBC patients.

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