scholarly journals A MicroRNA Component of the Neoplastic Microenvironment: Microregulators with Far-Reaching Impact

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaolei Li ◽  
Zhiqiang Wu ◽  
Xiaobing Fu ◽  
Weidong Han
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Tumor Development ◽  
Related Gene ◽  
Biological Mechanisms ◽  
Aberrant Expression ◽  
Small Noncoding Rnas ◽  
Cancer Related Gene ◽  
Microenvironmental Factors

The interplay between tumor cells and their microenvironment plays a pivotal role in tumor development and progression. Although a growing body of evidence has established the importance of the tumor microenvironment, an understanding of the crosstalk between its components and cancer cells remains elusive. The pathways triggered by microenvironmental factors could modulate cancer-related gene transcription, also affecting small noncoding RNAs, microRNAs, which have emerged as key posttranscriptional regulators of gene expression, directly involved in human cancers. Although microRNAs regulate most biological mechanisms, their role in the tumor microenvironment has only recently become the focus of intense research. In this paper, we focus on the intertwined connection between the tumor microenvironment and aberrant expression of microRNAs involved in carcinogenesis. We also discuss the emerging roles of microRNAs in the tumor microenvironment as it relates to cancer progression. We conclude that microRNAs are critical for our understanding of the development of cancer, and that targeting microRNA signaling pathways in the microenvironment as well as in tumor cells opens new therapeutic avenues to the global control of cancer.

scholarly journals The Roles of Stroma-Derived Chemokine in Different Stages of Cancer Metastases

2020 ◽  
Vol 11 ◽  
Author(s):  
Shahid Hussain ◽  
Bo Peng ◽  
Mathew Cherian ◽  
Jonathan W. Song ◽  
Dinesh K. Ahirwar ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Tumor Development ◽  
Inflammatory Cells ◽  
Host Cells ◽  
Metastatic Niche ◽  
Cancer Pathogenesis ◽  
Cancer Metastases ◽  
Cellular Components

The intricate interplay between malignant cells and host cellular and non-cellular components play crucial role in different stages of tumor development, progression, and metastases. Tumor and stromal cells communicate to each other through receptors such as integrins and secretion of signaling molecules like growth factors, cytokines, chemokines and inflammatory mediators. Chemokines mediated signaling pathways have emerged as major mechanisms underlying multifaceted roles played by host cells during tumor progression. In response to tumor stimuli, host cells-derived chemokines further activates signaling cascades that support the ability of tumor cells to invade surrounding basement membrane and extra-cellular matrix. The host-derived chemokines act on endothelial cells to increase their permeability and facilitate tumor cells intravasation and extravasation. The tumor cells-host neutrophils interaction within the vasculature initiates chemokines driven recruitment of inflammatory cells that protects circulatory tumor cells from immune attack. Chemokines secreted by tumor cells and stromal immune and non-immune cells within the tumor microenvironment enter the circulation and are responsible for formation of a “pre-metastatic niche” like a “soil” in distant organs whereby circulating tumor cells “seed’ and colonize, leading to formation of metastatic foci. Given the importance of host derived chemokines in cancer progression and metastases several drugs like Mogamulizumab, Plerixafor, Repertaxin among others are part of ongoing clinical trial which target chemokines and their receptors against cancer pathogenesis. In this review, we focus on recent advances in understanding the complexity of chemokines network in tumor microenvironment, with an emphasis on chemokines secreted from host cells. We especially summarize the role of host-derived chemokines in different stages of metastases, including invasion, dissemination, migration into the vasculature, and seeding into the pre-metastatic niche. We finally provide a brief description of prospective drugs that target chemokines in different clinical trials against cancer.

scholarly journals Biological mechanisms linked to inflammation in cancer: Discovery of tumor microenvironment-related biomarkers and their clinical application in solid tumors

2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 8-11 ◽  
Author(s):  
Paola Nisticò ◽  
Gennaro Ciliberto
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Tumor Development ◽  
Short Paper ◽  
Great Relevance ◽  
Cellular Components ◽  
The Relationship

Our view of cancer biology radically shifted from a “cancer-cell-centric” vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.

scholarly journals microRNAs in the Antitumor Immune Response and in Bone Metastasis of Breast Cancer: From Biological Mechanisms to Therapeutics

2020 ◽  
Vol 21 (8) ◽  
pp. 2805 ◽  
Author(s):  
Marta Gomarasca ◽  
Paola Maroni ◽  
Giuseppe Banfi ◽  
Giovanni Lombardi
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Formation Process ◽  
Immune Escape ◽  
Antitumor Immune Response ◽  
Metastasis Formation ◽  
Biological Mechanisms ◽  
Aberrant Expression

Breast cancer is the most common type of cancer in women, and the occurrence of metastasis drastically worsens the prognosis and reduces overall survival. Understanding the biological mechanisms that regulate the transformation of malignant cells, the consequent metastatic transformation, and the immune surveillance in the tumor progression would contribute to the development of more effective and targeted treatments. In this context, microRNAs (miRNAs) have proven to be key regulators of the tumor-immune cells crosstalk for the hijack of the immunosurveillance to promote tumor cells immune escape and cancer progression, as well as modulators of the metastasis formation process, ranging from the preparation of the metastatic site to the transformation into the migrating phenotype of tumor cells. In particular, their deregulated expression has been linked to the aberrant expression of oncogenes and tumor suppressor genes to promote tumorigenesis. This review aims at summarizing the role and functions of miRNAs involved in antitumor immune response and in the metastasis formation process in breast cancer. Additionally, miRNAs are promising targets for gene therapy as their modulation has the potential to support or inhibit specific mechanisms to negatively affect tumorigenesis. With this perspective, the most recent strategies developed for miRNA-based therapeutics are illustrated.

scholarly journals The Roles of CD38 and CD157 in the Solid Tumor Microenvironment and Cancer Immunotherapy

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 26 ◽  
Author(s):  
Yu Jun Wo ◽  
Adelia Shin Ping Gan ◽  
Xinru Lim ◽  
Isabel Shu Ying Tay ◽  
Sherlly Lim ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Solid Tumor ◽  
Immune Cells ◽  
Tumor Development ◽  
Cancer Prognosis ◽  
Immune Resistance ◽  
Tumor Types

The tumor microenvironment (TME) consists of extracellular matrix proteins, immune cells, vascular cells, lymphatics and fibroblasts. Under normal physiological conditions, tissue homeostasis protects against tumor development. However, under pathological conditions, interplay between the tumor and its microenvironment can promote tumor initiation, growth and metastasis. Immune cells within the TME have an important role in the formation, growth and metastasis of tumors, and in the responsiveness of these tumors to immunotherapy. Recent breakthroughs in the field of cancer immunotherapy have further highlighted the potential of targeting TME elements, including these immune cells, to improve the efficacy of cancer prognostics and immunotherapy. CD38 and CD157 are glycoproteins that contribute to the tumorigenic properties of the TME. For example, in the hypoxic TME, the enzymatic functions of CD38 result in an immunosuppressive environment. This leads to increased immune resistance in tumor cells and allows faster growth and proliferation rates. CD157 may also aid the production of an immunosuppressive TME, and confers increased malignancy to tumor cells through the promotion of tumor invasion and metastasis. An improved understanding of CD38 and CD157 in the TME, and how these glycoproteins affect cancer progression, will be useful to develop both cancer prognosis and treatment methods. This review aims to discuss the roles of CD38 and CD157 in the TME and cancer immunotherapy of a range of solid tumor types.

scholarly journals Hypoxia-inducible factor (HIF): fuel for cancer progression

2021 ◽  
Vol 14 ◽  
Author(s):  
Saurabh Satija ◽  
Harpreet Kaur ◽  
Murtaza M. Tambuwala ◽  
Prabal Sharma ◽  
Manish Vyas ◽  
...  
Keyword(s):  
Biological Sciences ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Oxygen Deficiency ◽  
Hypoxia Inducible Factor ◽  
Transcription Factor Activation ◽  
Underlying Mechanisms ◽  
Adaptive Reactions

Hypoxia is an integral part of tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1β (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygen-independent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mchanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors.

scholarly journals Tumor Microenvironment and Cell Fusion

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Erhui Jiang ◽  
Tinglin Yan ◽  
Zhi Xu ◽  
Zhengjun Shang
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Fusion ◽  
Direct Interaction ◽  
Tumor Stem Cell ◽  
Migration And Invasion ◽  
Future Research ◽  
Microenvironmental Factors ◽  
Cell Cell

Cell fusion is a highly regulated biological process that occurs under both physiological and pathological conditions. The cellular and extracellular environment is critical for the induction of the cell–cell fusion. Aberrant cell fusion is initiated during tumor progression. Tumor microenvironment is a complex dynamic system formed by the interaction between tumor cells and their surrounding cells. Cell–cell fusion mediates direct interaction between tumor cells and their surrounding cells and is associated with tumor initiation and progression. Various microenvironmental factors affect cell fusion in tumor microenvironment and generate hybrids that acquire genomes of both parental cells and exhibit novel characteristics, such as tumor stem cell-like properties, radioresistance, drug resistance, immune evasion, and enhanced migration and invasion abilities, which are closely related to the initiation, invasion, and metastasis of tumor. The phenotypic characteristics of hybrids are based on the phenotypes of parental cells, and the fusion of tumor cells with diverse types of microenvironmental fusogenic cells is concomitant with phenotypic heterogeneity. This review highlights the types of fusogenic cells in tumor microenvironment that can fuse with tumor cells and their specific significance and summarizes the various microenvironmental factors affecting tumor cell fusion. This review may be used as a reference to develop strategies for future research on tumor cell fusion and the exploration of cell fusion-based antitumor therapies.

scholarly journals NKG2D signaling regulates IL-17A-producing γδT cells to promote cancer progression

2021 ◽  
Author(s):  
Sophie Curio ◽  
Sarah C Edwards ◽  
Toshiyasu Suzuki ◽  
Jenny McGovern ◽  
Chiara Triulzi ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Cell Activation ◽  
Tumor Development ◽  
Cell Receptor ◽  
Dependent Manner ◽  
Γδt Cells ◽  
Γδt Cell

γδT cells are unconventional T cells particularly abundant in mucosal tissues that play an important role in tissue surveillance and homeostasis. γδT cell activation is mediated by the T cell receptor composed of γ and δ chains, as well as activating receptors for stress-induced ligands, such as NKG2D. Contrary to the well-established anti-tumor function of γδT cells, recent studies have shown that γδT cells can promote tumor development in certain contexts. However, the mechanisms leading to this disease-promoting role remain poorly understood. Here, we show that mice lacking γδT cells survive longer in a mouse model of intestinal cancer, further supporting their pro-tumoral role. In a surprising conceptual twist, we found that these pro-tumor γδT cells are regulated by NKG2D signaling, a receptor normally associated with cancer cell killing. Germline deletion of Klrk1, the gene encoding NKG2D, reduced the frequency of γδT cells in the tumor microenvironment and delayed tumor progression. We further show that blocking NKG2D reduces the capability of γδT cells to produce IL-17A in the pre-metastatic lung and that co-culture of lung T cells with NKG2D ligand-expressing tumor cells specifically increases the frequency of γδT cells. Together, these data support the hypothesis that in a tumor microenvironment where NKG2D ligands are constitutively expressed, γδT cells accumulate in an NKG2D-dependent manner and drive tumor progression by secreting pro-inflammatory cytokines, such as IL-17A.

scholarly journals The CAFs Related Gene CALD1 Is a Prognostic Biomarker and Correlated With Immune Infiltration in Bladder Cancer

2021 ◽  
Author(s):  
YiHeng Du ◽  
Xiang Jiang ◽  
Bo Wang ◽  
Jin Cao ◽  
Yi Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Strong Association ◽  
Interaction Network ◽  
Clinical Samples ◽  
Related Gene ◽  
Expression Of Genes ◽  
Depth Analysis

Abstract Background: Stromal components of the tumor microenvironment contribute to bladder cancer progression, and Cancer-Associated Fibroblasts (CAFs) were reported to play an important role. Accumulating pieces of evidence indicate that CAFs participate in the crosstalk with tumor cells and have a complex interaction network with immune components. Further study of the role of CAFs in the bladder cancer microenvironment and the search for possible specific markers are important for a deeper understanding of the roles of CAFs in bladder cancer progression and immunomodulation.Methods: In the present study, we examined the abundance of CAFs in the TCGA and GEO datasets using the MCP-Counter algorithm. Additionally, the expression of genes related to CAFs was analyzed through the Weighted Gene Co-expression Network Analysis (WGCNA). The CIBERSORT and ESTIMATE algorithms were used for the correlation analysis between the key CAFs related gene and the tumor microenvironment components.Immunohistochemistry analysis in clinical samples was used to validate the results of bioinformatics analysis.Results: The results showed that CAFs were closely associated with the progression and prognosis of bladder cancer. WGCNA also revealed that CALD1 was a key gene significantly associated with CAFs in bladder cancer. Moreover, the further in-depth analysis showed that CALD1 significantly affected the progression and prognosis of bladder cancer. The CIBERSORT and ESTIMATE algorithms significant correlations between CALD1 and the tumor microenvironment components, including CAFs, macrophages, T cells, and multiple immune checkpoint related genes. Finally, immunohistochemistry results of clinical samples' validated the strong association between CALD1, CAFs, and macrophages.Conclusions: In the present study, we confirmed the cancer-promoting roles of CAFs in bladder cancer. Being a key gene associated with CAFs, CALD1 may promote bladder cancer progression by remodeling the tumor microenvironment. The bioinformatics methods, including the CIBERSORT, MCP-COUNTER and ESTIMATE algorithms, may provide important value for studying the tumor microenvironment.

scholarly journals LncRNA JPX promotes cervical cancer progression by modulating miR-25-3p/SOX4 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xia Chen ◽  
Jingxiu Yang ◽  
Yuping Wang
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Hela Cells ◽  
Noncoding Rna ◽  
Tumor Development ◽  
Tumor Xenograft ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Aberrant Expression

Abstract Background The long noncoding RNA (lncRNA) JPX is a molecular switch for X-chromosome inactivation. Accumulating studies have shown that the aberrant expression and function of lncRNAs are involved in the occurrence and development of tumors. However, the functional importance and mechanism of the action of lncRNA JPX in cervical cancer (CC) remain unknown. Method In this study, qRT-PCR and western blotting were used to evaluate the mRNA or protein expression of JPX, miR-25-3p and SOX4 in CC tissues and cell lines. StarBase v2.0 database, luciferase reporter assay and RNA immunoprecipitation assay were used to explore the relationship between JPX and miR-25-3p. EdU assay, CCK-8 assay and transwell assay were utilized to evaluate the proliferation, migration and invasion of CC cells. The tumor xenograft assay in nude mice was performed to demonstrate the role of the JPX/miR-25-3p/SOX4 axis in CC. Results We found that JPX was markedly upregulated, whereas miR-25-3p was markedly downregulated in CC tissues and cell lines, and the expression of JPX was negatively correlated with miR-25-3p in CC tissues. Moreover, overexpression of JPX increased proliferation, migration and invasion of HeLa cells, whereas knockdown of JPX decreased proliferation, migration and invasion of HeLa cells. In contrast to JPX, overexpression of miR-25-3p decreased proliferation, migration and invasion of HeLa cells. In addition, knockdown of JPX was found to inhibit HeLa cell viability and tumor development via up-regulating the expression of miR-25-3p and inhibiting the expression of SOX4. Conclusions Our study demonstrates that JPX promotes cervical cancer progression through modulating the miR-25-3p/SOX4 axis, and may serve as a potential target for CC therapy.

scholarly journals The role of microenvironment in tumor angiogenesis

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Xianjie Jiang ◽  
Jie Wang ◽  
Xiangying Deng ◽  
Fang Xiong ◽  
Shanshan Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Tumor Angiogenesis ◽  
Tumor Development ◽  
Invasion And Metastasis ◽  
Growth And Survival ◽  
Survival And Development ◽  
Inflammatory Drugs ◽  
Conducive Environment

Abstract Tumor angiogenesis is necessary for the continued survival and development of tumor cells, and plays an important role in their growth, invasion, and metastasis. The tumor microenvironment—composed of tumor cells, surrounding cells, and secreted cytokines—provides a conducive environment for the growth and survival of tumors. Different components of the tumor microenvironment can regulate tumor development. In this review, we have discussed the regulatory role of the microenvironment in tumor angiogenesis. High expression of angiogenic factors and inflammatory cytokines in the tumor microenvironment, as well as hypoxia, are presumed to be the reasons for poor therapeutic efficacy of current anti-angiogenic drugs. A combination of anti-angiogenic drugs and antitumor inflammatory drugs or hypoxia inhibitors might improve the therapeutic outcome.

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