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 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 Computational staining of pathology images to study tumor microenvironment in lung cancer

2019 ◽  
Author(s):  
Shidan Wang ◽  
Ruichen Rong ◽  
Donghan M. Yang ◽  
Ling Cai ◽  
Lin Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Microenvironment ◽  
Spatial Organization ◽  
Risk Group ◽  
Biological Pathways ◽  
The Cancer Genome Atlas ◽  
Analysis Tool ◽  
Cell Nuclei ◽  
Tumor Tissues ◽  
Different Types

ABSTRACTThe spatial organization of different types of cells in tumor tissues reveals important information about the tumor microenvironment (TME). In order to facilitate the study of cellular spatial organization and interactions, we developed a comprehensive nuclei segmentation and classification tool to characterize the TME from standard Hematoxylin and Eosin (H&E)-stained pathology images. This tool can computationally “stain” different types of cell nuclei in H&E pathology images to facilitate pathologists in analyzing the TME.A Mask Regional-Convolutional Neural Network (Mask-RCNN) model was developed to segment the nuclei of tumor, stromal, lymphocyte, macrophage, karyorrhexis and red blood cells in lung adenocarcinoma (ADC). Using this tool, we identified and classified cell nuclei and extracted 48 cell spatial organization-related features that characterize the TME. Using these features, we developed a prognostic model from the National Lung Screening Trial dataset, and independently validated the model in The Cancer Genome Atlas (TCGA) lung ADC dataset, in which the predicted high-risk group showed significantly worse survival than the low-risk group (pv= 0.001), with a hazard ratio of 2.23 [1.37-3.65] after adjusting for clinical variables. Furthermore, the image-derived TME features were significantly correlated with the gene expression of biological pathways. For example, transcription activation of both the T-cell receptor (TCR) and Programmed cell death protein 1 (PD1) pathways was positively correlated with the density of detected lymphocytes in tumor tissues, while expression of the extracellular matrix organization pathway was positively correlated with the density of stromal cells.This study developed a deep learning-based analysis tool to dissect the TME from tumor tissue images. Using this tool, we demonstrated that the spatial organization of different cell types is predictive of patient survival and associated with the gene expression of biological pathways. Although developed from the pathology images of lung ADC, this model can be adapted into other types of cancers.

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 WHEN TO CALL THE CUSTOMER? TIMING OF CUSTOMER INVOLVEMENT IN THE DEVELOPMENT OF NEW PRODUCTS AND SERVICES

2019 ◽  
Vol 23 (01) ◽  
pp. 1950055
Author(s):  
SABIT VESELAJ ◽  
MAGNUS THOR TORFASON
Keyword(s):  
New Products ◽  
Large Body ◽  
Project Performance ◽  
Customer Needs ◽  
Customer Involvement ◽  
Early Stages ◽  
Different Types

Involving customers in the development of new products and services helps firms understand customer needs, increasing the likelihood of meeting those needs and expectations. Although a large body of literature addresses the implications of customer involvement for project performance, the results of previous research are somewhat inconsistent. This paper explores this issue by examining the differing impact of customer involvement on the development of new products and new services. We propose that the role of customer involvement differs for these two types of innovations, with involvement in the early stages more important for products and involvement in the launch stage more important for services. Our results, based on a comprehensive dataset on customer involvement in innovation, are consistent with such a pattern, suggesting that more attention should be paid to the conditional benefits of customer involvement in different types of solution development.

scholarly journals The Dual Role of TAM Receptors in Autoimmune Diseases and Cancer: An Overview

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 166 ◽  
Author(s):  
Martha Wium ◽  
Juliano Paccez ◽  
Luiz Zerbini
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Tyrosine Kinases ◽  
Therapeutic Potential ◽  
Cellular Processes ◽  
Tam Receptors ◽  
Different Types ◽  
Extracellular Environment ◽  
Migration And Development

Receptor tyrosine kinases (RTKs) regulate cellular processes by converting signals from the extracellular environment to the cytoplasm and nucleus. Tyro3, Axl, and Mer (TAM) receptors form an RTK family that plays an intricate role in tissue maintenance, phagocytosis, and inflammation as well as cell proliferation, survival, migration, and development. Defects in TAM signaling are associated with numerous autoimmune diseases and different types of cancers. Here, we review the structure of TAM receptors, their ligands, and their biological functions. We discuss the role of TAM receptors and soluble circulating TAM receptors in the autoimmune diseases systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Lastly, we discuss the effect of TAM receptor deregulation in cancer and explore the therapeutic potential of TAM receptors in the treatment of diseases.

scholarly journals Role of PRKDC in cancer initiation, progression, and treatment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Chen ◽  
Yi Li ◽  
Jiani Xiong ◽  
Bin Lan ◽  
Xuefeng Wang ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Double Strand Breaks ◽  
Nonhomologous End Joining ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Strand Breaks ◽  
Cancer Initiation ◽  
Different Types ◽  
Dependent Protein

AbstractThe PRKDC gene encodes the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) protein. DNA-PKcs plays an important role in nonhomologous end joining (NHEJ) of DNA double-strand breaks (DSBs) and is also closely related to the establishment of central immune tolerance and the maintenance of chromosome stability. The occurrence and development of different types of tumors and the results of their treatment are also influenced by DNA-PKcs, and it may also predict the results of radiotherapy, chemotherapy, and therapy with immune checkpoint inhibitors (ICIs). Here, we discuss and review the structure and mechanism of action of PRKDC and DNA-PKcs and their relationship with cancer.

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 Targeting the CD47-SIRPα signaling axis: current studies on B-cell lymphoma immunotherapy

2018 ◽  
Vol 46 (11) ◽  
pp. 4418-4426 ◽  
Author(s):  
Jin Zhang ◽  
Shenhe Jin ◽  
Xiaojun Guo ◽  
Wenbin Qian
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immunoglobulin Superfamily ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Cancer Initiation ◽  
Different Types ◽  
Signaling Axis ◽  
Tumor Growth And Metastasis

The function of the immune system in cancer initiation and progression has been widely examined. Notably, immunotherapy has become a promising approach for cancer treatment. CD47, a member of the immunoglobulin superfamily, plays an important role in the immune regulation of cancer by binding to SIRPα. Multiple studies have detected high CD47 expression on the surface of tumor cells, which indicates poor prognosis. Treatments that block the interaction of CD47 and SIRPα significantly suppress tumor growth and metastasis through diverse mechanisms, such as phagocytosis, antibody-dependent cellular cytotoxicity, and apoptosis. Recently, several studies have reported increased CD47 expression on different types of lymphoma cells, indicating that the CD47-SIRPα pathway can be used as a therapeutic target in lymphoma. This review focuses on the role of CD47-SIRPα in B-cell lymphoma and discusses promising therapeutic strategies targeting the CD47-SIRPα axis, which yield insights into the immunotherapy of B-cell lymphoma.

scholarly journals Regulatory Roles of Six-Transmembrane Epithelial Antigen of the Prostate Family Members in the Occurrence and Development of Malignant Tumors

2021 ◽  
Vol 9 ◽  
Author(s):  
Wen-Jia Chen ◽  
Hua-Tao Wu ◽  
Chun-Lan Li ◽  
Yi-Ke Lin ◽  
Ze-Xuan Fang ◽  
...  
Keyword(s):  
Immune Response ◽  
Theoretical Basis ◽  
Malignant Tumors ◽  
Expression Patterns ◽  
Molecular Transport ◽  
Therapeutic Resistance ◽  
Biological Processes ◽  
Different Types ◽  
And Function

The human six-transmembrane epithelial antigen of the prostate (STEAP) proteins, which include STEAP1–4 and atypical STEAP1B, contain six transmembrane domains and are located in the cell membrane. STEAPs are considered archaeal metal oxidoreductases, based on their heme groups and F420H2:NADP+ oxidoreductase (FNO)-like structures, and play an important role in cell metal metabolism. Interestingly, STEAPs not only participate in biological processes, such as molecular transport, cell cycling, immune response, and intracellular and extracellular activities, but also are closely related to the occurrence and development of several diseases, especially malignant tumors. Up to now, the expression patterns of STEAPs have been found to be diverse in different types of tumors, with controversial participation in different aspects of malignancy, such as cell proliferation, migration, invasion, apoptosis, and therapeutic resistance. It is clinically important to explore the potential roles of STEAPs as new immunotherapeutic targets for the treatment of different malignant tumors. Therefore, this review focuses on the molecular mechanism and function of STEAPs in the occurrence and development of different cancers in order to understand the role of STEAPs in cancer and provide a new theoretical basis for the treatment of diverse cancers.

Nanotherapy Targeting the Tumor Microenvironment

2019 ◽  
Vol 19 (7) ◽  
pp. 525-533 ◽  
Author(s):  
Bo-Shen Gong ◽  
Rui Wang ◽  
Hong-Xia Xu ◽  
Ming-Yong Miao ◽  
Zhen-Zhen Yao
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Necessary Conditions ◽  
Rapid Development ◽  
Therapeutic Effects ◽  
Tumor Resistance ◽  
Invasion And Metastasis ◽  
Passive Targeting ◽  
Different Types

Cancer is characterized by high mortality and low curability. Recent studies have shown that the mechanism of tumor resistance involves not only endogenous changes to tumor cells, but also to the tumor microenvironment (TME), which provides the necessary conditions for the growth, invasion, and metastasis of cancer cells, akin to Stephen Paget’s hypothesis of “seed and soil.” Hence, the TME is a significant target for cancer therapy via nanoparticles, which can carry different kinds of drugs targeting different types or stages of tumors. The key step of nanotherapy is the achievement of accurate active or passive targeting to trigger drugs precisely at tumor cells, with less toxicity and fewer side effects. With deepened understanding of the tumor microenvironment and rapid development of the nanomaterial industry, the mechanisms of nanotherapy could be individualized according to the specific TME characteristics, including low pH, cancer-associated fibroblasts (CAFs), and increased expression of metalloproteinase. However, some abnormal features of the TME limit drugs from reaching all tumor cells in lethal concentrations, and the characteristics of tumors vary in numerous ways, resulting in great challenges for the clinical application of nanotherapy. In this review, we discuss the essential role of the tumor microenvironment in the genesis and development of tumors, as well as the measures required to improve the therapeutic effects of tumor microenvironment-targeting nanoparticles and ways to reduce damage to normal tissue.

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