scholarly journals Unexpected guests in the tumor microenvironment: microbiome in cancer

2020 ◽  
Author(s):  
Abigail Wong-Rolle ◽  
Haohan Karen Wei ◽  
Chen Zhao ◽  
Chengcheng Jin
Keyword(s):  
Gastrointestinal Tract ◽  
Tumor Microenvironment ◽  
Therapeutic Response ◽  
Intestinal Microbiome ◽  
Cancer Development ◽  
Tumor Type ◽  
Mechanistic Studies ◽  
Comprehensive Review ◽  
Cancer Initiation

AbstractAlthough intestinal microbiome have been established as an important biomarker and regulator of cancer development and therapeutic response, less is known about the role of microbiome at other body sites in cancer. Emerging evidence has revealed that the local microbiota make up an important part of the tumor microenvironment across many types of cancer, especially in cancers arising from mucosal sites, including the lung, skin and gastrointestinal tract. The populations of bacteria that reside specifically within tumors have been found to be tumor-type specific, and mechanistic studies have demonstrated that tumor-associated microbiota may directly regulate cancer initiation, progression and responses to chemo- or immuno-therapies. This review aims to provide a comprehensive review of the important literature on the microbiota in the cancerous tissue, and their function and mechanism of action in cancer development and treatment.

scholarly journals MicroRNAs as Emerging Regulators of Signaling in the Tumor Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 911 ◽  
Author(s):  
Shahzad Nawaz Syed ◽  
Bernhard Brüne
Keyword(s):  
Tumor Microenvironment ◽  
Signaling Pathways ◽  
Target Identification ◽  
Cancer Therapeutics ◽  
Protein Translation ◽  
Transcriptional Gene Silencing ◽  
Post Transcriptional Gene Silencing ◽  
Cancer Initiation ◽  
Regulate Protein

A myriad of signaling molecules in a heuristic network of the tumor microenvironment (TME) pose a challenge and an opportunity for novel therapeutic target identification in human cancers. MicroRNAs (miRs), due to their ability to affect signaling pathways at various levels, take a prominent space in the quest of novel cancer therapeutics. The role of miRs in cancer initiation, progression, as well as in chemoresistance, is being increasingly investigated. The canonical function of miRs is to target mRNAs for post-transcriptional gene silencing, which has a great implication in first-order regulation of signaling pathways. However, several reports suggest that miRs also perform non-canonical functions, partly due to their characteristic non-coding small RNA nature. Examples emerge when they act as ligands for toll-like receptors or perform second-order functions, e.g., to regulate protein translation and interactions. This review is a compendium of recent advancements in understanding the role of miRs in cancer signaling and focuses on the role of miRs as novel regulators of the signaling pathway in the TME.

scholarly journals Chronic Hexavalent Chromium Exposure Induces Cancer Stem Cell-Like Property and Tumorigenesis by Increasing c-Myc Expression

2019 ◽  
Vol 172 (2) ◽  
pp. 252-264 ◽  
Author(s):  
Zhishan Wang ◽  
Hsuan-Pei Lin ◽  
Yunfei Li ◽  
Hua Tao ◽  
Ping Yang ◽  
...  
Keyword(s):  
Hexavalent Chromium ◽  
Low Dose ◽  
Cell Transformation ◽  
Mechanistic Studies ◽  
Human Bronchial Epithelial Cells ◽  
Environmental Carcinogen ◽  
Bronchial Epithelial ◽  
Cancer Initiation ◽  
Chromium Exposure

Abstract Hexavalent chromium [Cr(VI)] is one of the most common environmental carcinogen causing lung cancer in humans; however, the mechanism of Cr(VI) carcinogenesis remains elusive. Cancer stem cells (CSCs) are considered as cancer initiating and maintaining cells. Ours and other recent studies showed that chronic Cr(VI) exposure induces CSC-like property representing an important mechanism of Cr(VI) carcinogenesis. However, how Cr(VI) exposure induces CSC-like property remains largely unknown. In this study, we found that stably knocking down the expression of c-Myc, a proto-oncogene and one of key stemness factors playing critical roles in cancer initiation and progression, in Cr(VI)-transformed human bronchial epithelial cells [BEAS-2B-Cr(VI)] significantly decreased their CSC-like property and tumorigenicity in mice. Moreover, stably knocking down c-Myc expression in parental nontransformed BEAS-2B cells significantly impaired the capability of chronic Cr(VI) exposure to induce CSC-like property and cell transformation. It was also found that stably overexpressing c-Myc alone in parental nontransformed BEAS-2B cells is capable of causing CSC-like property and cell transformation. Mechanistic studies showed that chronic Cr(VI) exposure increases c-Myc expression by down-regulating the level of microRNA-494 (miR-494). It was further determined that overexpressing miR-494 significantly reduces Cr(VI)-induced CSC-like property, cell transformation, and tumorigenesis mainly through down-regulating c-Myc expression. Together, these findings indicate that chronic low dose Cr(VI) exposure induces CSC-like property and tumorigenesis by increasing c-Myc expression through down-regulating the level of miR-494, revealing an important role of the proto-oncogene c-Myc in Cr(VI) carcinogenesis.

Targeting Tumor-derived exosomes expressing CD73: new opportunities in the pathogenesis and treatment of cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Vajihe Taghdiri Nooshabadi ◽  
Samaneh Arab
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Cancer Development ◽  
Therapeutic Resistance ◽  
Intracellular Communication ◽  
Different Types ◽  
Therapeutic Protocols ◽  
Tumor Exosomes ◽  
Selection Of

: Tumor-derived exosomes contain biological contents such as proteins, lipids, RNA (miRNAs, mRNAs, lncRNA), and DNA for intracellular communication. Meanwhile, studies have shown the role of exosomes in cancer progression, metastasis, and therapeutic resistance. Furthermore, tumor exosomes have received growing attention due to their potential as novel therapeutic protocols for the treatment of cancers. Adenosine nucleoside, which is a derivative of ATP, is highly elevated in the tumor microenvironment by CD39 and CD73 enzymatic activity. Recently, it is distinguished that cancer cellderived exosomes carry CD39 and CD73 on their surface and may contribute to rising adenosine levels in the tumor microenvironment. In this review, we summarize the evidence of CD39/CD73-bearing exosomes and their role in cancer development, progression, invasion, angiogenesis, metastasis and their application in the selection of the appropriate strategy to treat different types of cancer.

scholarly journals How Do Cytokines Trigger Genomic Instability?

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Ioannis L. Aivaliotis ◽  
Ioannis S. Pateras ◽  
Marilena Papaioannou ◽  
Christina Glytsou ◽  
Konstantinos Kontzoglou ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Genomic Instability ◽  
The Other ◽  
Cancer Development ◽  
Tumor Initiation ◽  
Dual Effect ◽  
Other Hand ◽  
Shed Light ◽  
Comprehensive Study

Inflammation is a double-edged sword presenting a dual effect on cancer development, from one hand promoting tumor initiation and progression and from the other hand protecting against cancer through immunosurveillance mechanisms. Cytokines are crucial components of inflammation, participating in the interaction between the cells of tumor microenvironment. A comprehensive study of the role of cytokines in the context of the inflammation-tumorigenesis interplay helps us to shed light in the pathogenesis of cancer. In this paper we focus on the role of cytokines in the development of genomic instability, an evolving hallmark of cancer.

scholarly journals Tackling tumor microenvironment through epigenetic tools to improve cancer immunotherapy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Iris Lodewijk ◽  
Sandra P. Nunes ◽  
Rui Henrique ◽  
Carmen Jerónimo ◽  
Marta Dueñas ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Immune Cells ◽  
Cancer Development ◽  
Main Body ◽  
Tumor Type ◽  
Epigenetic Alterations ◽  
Epigenetic Biomarkers ◽  
Epigenetic Machinery ◽  
The Impact

Abstract Background Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development. Moreover, immunotherapy is briefly discussed in the context of epigenetics, describing both its combination with epigenetic drugs and the need for epigenetic biomarkers to predict response to immune checkpoint blockage. Main body Combining both topics, epigenetic machinery plays a central role in generating an immunosuppressive environment for cancer growth, which creates a barrier for immunotherapy to be successful. Furthermore, epigenetic-directed compounds may not only affect cancer cells but also immune cells in the tumor microenvironment, which could be beneficial for the clinical response to immunotherapy. Conclusion Thus, modulating epigenetics in combination with immunotherapy might be a promising therapeutic option to improve the success of this therapy. Further studies are necessary to (1) understand in depth the impact of the epigenetic machinery in the tumor microenvironment; (2) how the epigenetic machinery can be modulated according to tumor type to increase response to immunotherapy and (3) find reliable biomarkers for a better selection of patients eligible to immunotherapy.

scholarly journals The Janus-like role of proline metabolism in cancer

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Lynsey Burke ◽  
Inna Guterman ◽  
Raquel Palacios Gallego ◽  
Robert G. Britton ◽  
Daniel Burschowsky ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Essential Amino Acid ◽  
Oxygen Limitation ◽  
Tumor Type ◽  
Proline Metabolism ◽  
Proline Dehydrogenase ◽  
Comprehensive Review ◽  
Metabolism Enzymes ◽  
Carboxylate Reductase

Abstract The metabolism of the non-essential amino acid L-proline is emerging as a key pathway in the metabolic rewiring that sustains cancer cells proliferation, survival and metastatic spread. Pyrroline-5-carboxylate reductase (PYCR) and proline dehydrogenase (PRODH) enzymes, which catalyze the last step in proline biosynthesis and the first step of its catabolism, respectively, have been extensively associated with the progression of several malignancies, and have been exposed as potential targets for anticancer drug development. As investigations into the links between proline metabolism and cancer accumulate, the complexity, and sometimes contradictory nature of this interaction emerge. It is clear that the role of proline metabolism enzymes in cancer depends on tumor type, with different cancers and cancer-related phenotypes displaying different dependencies on these enzymes. Unexpectedly, the outcome of rewiring proline metabolism also differs between conditions of nutrient and oxygen limitation. Here, we provide a comprehensive review of proline metabolism in cancer; we collate the experimental evidence that links proline metabolism with the different aspects of cancer progression and critically discuss the potential mechanisms involved.

scholarly journals Abstract 3973: Role of thyroid tumor microenvironment secretome in cancer initiation and progression

2017 ◽  
Author(s):  
Neha Yashpal Tuli ◽  
Ameet Kamat ◽  
Rachana Maniyar ◽  
Ghada Ben Rahoma ◽  
Sanjukta Chakraborty ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Thyroid Tumor ◽  
Cancer Initiation

scholarly journals The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintaining

2021 ◽  
Author(s):  
Olga Kutova ◽  
Anton Pospelov ◽  
Irina Balalaeva
Keyword(s):  
Tumor Microenvironment ◽  
Purinergic Signaling ◽  
Large Body ◽  
Molecular Transport ◽  
Tumor Tissues ◽  
Cancer Initiation ◽  
Different Types ◽  
Channel Assembly ◽  
Extracellular Environment

The modern paradigm of studying the processes of carcinogenesis and vital activity of tumor tissues implies increased attention to constituents of tumor microenvironment (TME) and their interactions. These interactions between the cells in TME can be mediated via protein junctions of different types. Connexins (Cnxs) are one of the major contributors to intercellular communication. They form gap junctions responsible for the transfer of ions, metabolites, peptides, miRNA, etc. between neighboring tumor cells as well as between tumor and stromal cells. Cnx hemichannels mediate purinergic signaling and bidirectional molecular transport with the extracellular environment. Additionally, Cnxs were reported to localize in tumor-derived exosomes and facilitate the release of their cargo. A large body of evidence implies that the role of connexins in cancer is multifaceted. Pro- or anti-tumorigenic properties of connexins are determined by their abundance, localization and functionality as well as channel assembly and non-channel functions. In this review we have summarized the data on the Cnxs contribution in TME and to the cancer initiation and progression.

scholarly journals Importance of the alternative NF-κB activation pathway in inflammation-associated gastrointestinal carcinogenesis

2016 ◽  
Vol 310 (11) ◽  
pp. G1081-G1090 ◽  
Author(s):  
Yvette J. Merga ◽  
Adrian O'Hara ◽  
Michael D. Burkitt ◽  
Carrie A. Duckworth ◽  
Christopher S. Probert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gastrointestinal Tract ◽  
Signaling Pathway ◽  
Current Knowledge ◽  
Common Factor ◽  
Cancer Development ◽  
Gastrointestinal Malignancies ◽  
Activation Pathway ◽  
Inflammatory Bowel

Chronic inflammation is a common factor in the development of many gastrointestinal malignancies. Examples include inflammatory bowel disease predisposing to colorectal cancer, Barrett's esophagus as a precursor of esophageal adenocarcinoma, and Helicobacter pylori-induced gastric cancer. The classical activation pathway of NF-κB signaling has been identified as regulating several sporadic and inflammation-associated gastrointestinal tract malignancies. Emerging evidence suggests that the alternative NF-κB signaling pathway also exerts a distinct influence on these processes. This review brings together current knowledge of the role of the alternative NF-κB signaling pathway in the gastrointestinal tract, with a particular emphasis on inflammation-associated cancer development.

scholarly journals Role of inflammasomes and their regulators in prostate cancer initiation, progression and metastasis

2013 ◽  
Vol 18 (3) ◽  
Author(s):  
Sudhakar Veeranki
Keyword(s):  
Prostate Cancer ◽  
Older Men ◽  
Considerable Progress ◽  
Cancer Development ◽  
Successful Therapy ◽  
Effective Prevention ◽  
Cancer Initiation ◽  
Prevention And Treatment ◽  
Prostate Cancer Development

AbstractProstate cancer is one of the main cancers that affect men, especially older men. Though there has been considerable progress in understanding the progression of prostate cancer, the drivers of its development need to be studied more comprehensively. The emergence of resistant forms has also increased the clinical challenges involved in the treatment of prostate cancer. Recent evidence has suggested that inflammation might play an important role at various stages of cancer development. This review focuses on inflammasome research that is relevant to prostate cancer and indicates future avenues of study into its effective prevention and treatment through inflammasome regulation. With regard to prostate cancer, such research is still in its early stages. Further study is certainly necessary to gain a broader understanding of prostate cancer development and to create successful therapy solutions.

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