scholarly journals More Than an Adipokine: The Complex Roles of Chemerin Signaling in Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4778 ◽  
Author(s):  
Kerry B. Goralski ◽  
Ashley E. Jackson ◽  
Brendan T. McKeown ◽  
Christopher J. Sinal
Keyword(s):  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Cellular Differentiation ◽  
Target Cells ◽  
Immune Mediated ◽  
Promote Tumor Growth ◽  
Anti Cancer ◽  
Cancer Initiation ◽  
Tissue Production

Chemerin is widely recognized as an adipokine, with diverse biological roles in cellular differentiation and metabolism, as well as a leukocyte chemoattractant. Research investigating the role of chemerin in the obesity–cancer relationship has provided evidence both for pro- and anti-cancer effects. The tumor-promoting effects of chemerin primarily involve direct effects on migration, invasion, and metastasis as well as growth and proliferation of cancer cells. Chemerin can also promote tumor growth via the recruitment of tumor-supporting mesenchymal stromal cells and stimulation of angiogenesis pathways in endothelial cells. In contrast, the majority of evidence supports that the tumor-suppressing effects of chemerin are immune-mediated and result in a shift from immunosuppressive to immunogenic cell populations within the tumor microenvironment. Systemic chemerin and chemerin produced within the tumor microenvironment may contribute to these effects via signaling through CMKLR1 (chemerin1), GPR1 (chemerin2), and CCLR2 on target cells. As such, inhibition or activation of chemerin signaling could be beneficial as a therapeutic approach depending on the type of cancer. Additional studies are required to determine if obesity influences cancer initiation or progression through increased adipose tissue production of chemerin and/or altered chemerin processing that leads to changes in chemerin signaling in the tumor microenvironment.

scholarly journals Exploring the key communicator role of exosomes in cancer microenvironment through proteomics

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
HuiSu Kim ◽  
Dong Wook Kim ◽  
Je-Yoel Cho
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Diagnosis ◽  
Stromal Cells ◽  
Cancer Biology ◽  
Immune Surveillance ◽  
Cancer Microenvironment ◽  
Promote Tumor Growth ◽  
Therapeutic Tools ◽  
Intercellular Communications

ABSTRACT There have been many attempts to fully understand the mechanism of cancer behavior. Yet, how cancers develop and metastasize still remain elusive. Emerging concepts of cancer biology in recent years have focused on the communication of cancer with its microenvironment, since cancer cannot grow and live alone. Cancer needs to communicate with other cells for survival, and thus they secrete various messengers, including exosomes that contain many proteins, miRNAs, mRNAs, etc., for construction of the tumor microenvironment. Moreover, these intercellular communications between cancer and its microenvironment, including stromal cells or distant cells, can promote tumor growth, metastasis, and escape from immune surveillance. In this review, we summarized the role of proteins in the exosome as communicators between cancer and its microenvironment. Consequently, we present cancer specific exosome proteins and their unique roles in the interaction between cancer and its microenvironment. Clinically, these exosomes might provide useful biomarkers for cancer diagnosis and therapeutic tools for cancer treatment.

scholarly journals The Roles of Frequently Mutated Genes of Pancreatic Cancer in Regulation of Tumor Microenvironment

2020 ◽  
Vol 19 ◽  
pp. 153303382092096
Author(s):  
Hongzhi Sun ◽  
Bo Zhang ◽  
Haijun Li
Keyword(s):  
Tumor Microenvironment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Stromal Cells ◽  
Genomic Analysis ◽  
Ductal Adenocarcinoma ◽  
Genetic Mutations ◽  
Cellular Processes ◽  
Dismal Prognosis ◽  
Mutant Genes

Pancreatic ductal adenocarcinoma has extremely high malignancy and patients with pancreatic ductal adenocarcinoma have dismal prognosis. The failure of pancreatic ductal adenocarcinoma treatment is largely due to the tumor microenvironment, which is featured by ample stromal cells and complicated extracellular matrix. Recent genomic analysis revealed that pancreatic ductal adenocarcinoma harbors frequently mutated genes including KRAS, TP53, CDKN2A, and SMAD4, which can widely alter cellular processes and behaviors. As shown by accumulating studies, these mutant genes may also change tumor microenvironment, which in turn affects pancreatic ductal adenocarcinoma progression. In this review, we summarize the role of such genetic mutations in tumor microenvironment regulation and potential mechanisms.

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 The Role of Exosomal MicroRNAs in the Tumor Microenvironment of Breast Cancer

2019 ◽  
Vol 20 (16) ◽  
pp. 3884 ◽  
Author(s):  
Qingqing Liu ◽  
Fu Peng ◽  
Jianping Chen
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Breast Tissue ◽  
Cell Communication ◽  
Donor Cell ◽  
Intracellular Location ◽  
Non Coding Rna ◽  
Anti Cancer ◽  
Cell Sources

Breast cancer, ranking first among women’s cancers worldwide, develops from the breast tissue. Study of the breast tissue is, therefore of great significance to the diagnosis and treatment of breast cancer. Exosomes, acting as an effective communicator between cells, are in the ascendant in recent years. One of the most important cargoes contained in the exosomes is microRNAs, belonging to the non-coding RNA family. When the exosomal microRNAs are absorbed into the intracellular location, most of the microRNAs will act as tumor promoters or suppressors by inhibiting the translation process of the target mRNA, thus affecting the behavior of other stromal cells in the tumor microenvironment. At present, growing research focuses on the different types of donor cell sources, their contribution to cancer, miRNA profiling, their biomarker potential, etc. This review aims to state the function of diverse miRNAs in exosomes medicated cell–cell communication and the potency of some specific enriched miRNAs as molecular markers in clinical trials. We also describe the mechanism of anti-cancer compounds through exosomes and the exploration of artificially engineered techniques that lead miRNA-inhibitors into exosomes for therapeutic use.

scholarly journals Pancreatic Cancer and Cellular Senescence: Tumor Microenvironment under the Spotlight

2021 ◽  
Vol 23 (1) ◽  
pp. 254
Author(s):  
Michela Cortesi ◽  
Michele Zanoni ◽  
Francesca Pirini ◽  
Maria Maddalena Tumedei ◽  
Sara Ravaioli ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cellular Senescence ◽  
Cell Types ◽  
Research Field ◽  
Ductal Adenocarcinoma ◽  
Immune Mediated ◽  
Current Therapies ◽  
Cancerous Cells

Pancreatic ductal adenocarcinoma (PDAC) has one of the most dismal prognoses of all cancers due to its late manifestation and resistance to current therapies. Accumulating evidence has suggested that the malignant behavior of this cancer is mainly influenced by the associated strongly immunosuppressive, desmoplastic microenvironment and by the relatively low mutational burden. PDAC develops and progresses through a multi-step process. Early in tumorigenesis, cancer cells must evade the effects of cellular senescence, which slows proliferation and promotes the immune-mediated elimination of pre-malignant cells. The role of senescence as a tumor suppressor has been well-established; however, recent evidence has revealed novel pro-tumorigenic paracrine functions of senescent cells towards their microenvironment. Understanding the interactions between tumors and their microenvironment is a growing research field, with evidence having been provided that non-tumoral cells composing the tumor microenvironment (TME) influence tumor proliferation, metabolism, cell death, and therapeutic resistance. Simultaneously, cancer cells shape a tumor-supportive and immunosuppressive environment, influencing both non-tumoral neighboring and distant cells. The overall intention of this review is to provide an overview of the interplay that occurs between senescent and non-senescent cell types and to describe how such interplay may have an impact on PDAC progression. Specifically, the effects and the molecular changes occurring in non-cancerous cells during senescence, and how these may contribute to a tumor-permissive microenvironment, will be discussed. Finally, senescence targeting strategies will be briefly introduced, highlighting their potential in the treatment of PDAC.

scholarly journals Significance of a Tumor Microenvironment-Mediated P65-miR-30a-5p-BCL2L11 Amplification Loop in Multiple Myeloma

2021 ◽  
Author(s):  
Ling Xie ◽  
Xiuying Shi ◽  
Hongming Huang ◽  
Shaoqing Ju ◽  
Xudong Wang
Keyword(s):  
Multiple Myeloma ◽  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Molecular Mechanisms ◽  
Direct Interaction ◽  
Luciferase Reporter ◽  
Myeloma Cells ◽  
Amplification Loop

Abstract Despite significant progress in the treatment of myeloma, multiple myeloma (MM) remains an incurable hematological malignancy due to cell adhesion-mediated drug resistance (CAM-DR) phenotype. However, data on the molecular mechanisms underlying the CAM-DR remains scanty. Here, we identified a miRNA-mRNA regulatory network in myeloma cells that are directly adherent to bone marrow stromal cells (BMSCs). Our data showed that the BMSCs up-regulated miR-30a-5p and down-regulated BCL2L11 at both mRNA and protein level in the myeloma cells. Besides, luciferase reporter genes demonstrated direct interaction between miR-30a-5p and BCL2L11 gene. Moreover, the BMSCs activated NF-ΚB signaling pathway in myeloma cells and the NF-κB P65 was shown to directly bind the miR-30a-5p promoter region. Moreover, suppression of the miR-30a-5p or upregulation of the BCL2L11 promoted apoptosis of the myeloma cells independent of the BMSCs, thus suggesting clinical significance of miR-30a-5p inhibitor and PLBCL2L11 plasmid in CAM-DR. Together, our data demonstrated the role of P65-miR-30a-5p-BCL2L11 loop in CAM-DR myeloma cells. These findings give new insights into the role of tumor microenvironment in the treatment of patients with myeloma.

scholarly journals Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature

2021 ◽  
Vol 10 ◽  
Author(s):  
Aukie Hooglugt ◽  
Miesje M. van der Stoel ◽  
Reinier A. Boon ◽  
Stephan Huveneers
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Metastasis ◽  
Lymphatic Vessels ◽  
Cancer Therapies ◽  
Tumor Cell Growth ◽  
Vascular Normalization ◽  
Cancer Treatments ◽  
Anti Cancer ◽  
Tumor Endothelium

Solid tumors are dependent on vascularization for their growth. The hypoxic, stiff, and pro-angiogenic tumor microenvironment induces angiogenesis, giving rise to an immature, proliferative, and permeable vasculature. The tumor vessels promote tumor metastasis and complicate delivery of anti-cancer therapies. In many types of tumors, YAP/TAZ activation is correlated with increased levels of angiogenesis. In addition, endothelial YAP/TAZ activation is important for the formation of new blood and lymphatic vessels during development. Oncogenic activation of YAP/TAZ in tumor cell growth and invasion has been studied in great detail, however the role of YAP/TAZ within the tumor endothelium remains insufficiently understood, which complicates therapeutic strategies aimed at targeting YAP/TAZ in cancer. Here, we overview the upstream signals from the tumor microenvironment that control endothelial YAP/TAZ activation and explore the role of their downstream targets in driving tumor angiogenesis. We further discuss the potential for anti-cancer treatments and vascular normalization strategies to improve tumor therapies.

scholarly journals Targeting the Tumor Microenvironment in Neuroblastoma: Recent Advances and Future Directions

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2057 ◽  
Author(s):  
Shweta Joshi
Keyword(s):  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Stroma ◽  
Genetic Alterations ◽  
Future Directions ◽  
Pediatric Tumor ◽  
Normal Tissues ◽  
Recent Advances ◽  
Future Potential

Neuroblastoma (NB) is the most common pediatric tumor malignancy that originates from the neural crest and accounts for more than 15% of all the childhood deaths from cancer. The neuroblastoma cancer research has long been focused on the role of MYCN oncogene amplification and the contribution of other genetic alterations in the progression of this malignancy. However, it is now widely accepted that, not only tumor cells, but the components of tumor microenvironment (TME), including extracellular matrix, stromal cells and immune cells, also contribute to tumor progression in neuroblastoma. The complexity of different components of tumor stroma and their resemblance with surrounding normal tissues pose huge challenges for therapies targeting tumor microenvironment in NB. Hence, the detailed understanding of the composition of the TME of NB is crucial to improve existing and future potential immunotherapeutic approaches against this childhood cancer. In this review article, I will discuss different components of the TME of NB and the recent advances in the strategies, which are used to target the tumor microenvironment in neuroblastoma.

scholarly journals The Influence of Tumor Microenvironment on Immune Escape of Melanoma

2020 ◽  
Vol 21 (21) ◽  
pp. 8359 ◽  
Author(s):  
Aleksandra Simiczyjew ◽  
Ewelina Dratkiewicz ◽  
Justyna Mazurkiewicz ◽  
Marcin Ziętek ◽  
Rafał Matkowski ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Escape ◽  
Cell Types ◽  
Melanoma Cells ◽  
Cancer Therapies ◽  
System A ◽  
Anti Cancer ◽  
Low Efficiency ◽  
Inflammatory Molecules

The low efficiency of currently-used anti-cancer therapies poses a serious challenge, especially in the case of malignant melanoma, a cancer characterized by elevated invasiveness and relatively high mortality rate. The role of the tumor microenvironment in the progression of melanoma and its acquisition of resistance to treatment seems to be the main focus of recent studies. One of the factors that, in normal conditions, aids the organism in its fight against the cancer and, following the malignant transformation, adapts to facilitate the development of the tumor is the immune system. A variety of cell types, i.e., T and B lymphocytes, macrophages, and dendritic and natural killer cells, as well as neutrophils, support the growth and invasiveness of melanoma cells, utilizing a plethora of mechanisms, including secretion of pro-inflammatory molecules, induction of inhibitory receptors expression, or depletion of essential nutrients. This review provides a comprehensive summary of the processes regulated by tumor-associated cells that promote the immune escape of melanoma cells. The described mechanisms offer potential new targets for anti-cancer treatment and should be further studied to improve currently-employed therapies.

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