scholarly journals The role of microenvironment in tumor angiogenesis

Author(s):  
Xianjie Jiang ◽  
Jie Wang ◽  
Xiangying Deng ◽  
Fang Xiong ◽  
Shanshan Zhang ◽  
...  

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.

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 445 ◽  
Author(s):  
Javier Mora ◽  
Christina Mertens ◽  
Julia K. Meier ◽  
Dominik C. Fuhrmann ◽  
Bernhard Brüne ◽  
...  

The inflammatory tumor microenvironment is an important regulator of carcinogenesis. Tumor-infiltrating immune cells promote each step of tumor development, exerting crucial functions from initiation, early neovascularization, to metastasis. During tumor outgrowth, tumor-associated immune cells, including myeloid cells and lymphocytes, acquire a tumor-supportive, anti-inflammatory phenotype due to their interaction with tumor cells. Microenvironmental cues such as inflammation and hypoxia are mainly responsible for creating a tumor-supportive niche. Moreover, it is becoming apparent that the availability of iron within the tumor not only affects tumor growth and survival, but also the polarization of infiltrating immune cells. The interaction of tumor cells and infiltrating immune cells is multifaceted and complex, finally leading to different activation phenotypes of infiltrating immune cells regarding their functional heterogeneity and plasticity. In recent years, it was discovered that these phenotypes are mainly implicated in defining tumor outcome. Here, we discuss the role of the metabolic activation of both tumor cells and infiltrating immune cells in order to adapt their metabolism during tumor growth. Additionally, we address the role of iron availability and the hypoxic conditioning of the tumor with regard to tumor growth and we describe the relevance of therapeutic strategies to target such metabolic characteristics.


2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 8-11 ◽  
Author(s):  
Paola Nisticò ◽  
Gennaro Ciliberto

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.


2019 ◽  
Vol 19 (7) ◽  
pp. 525-533 ◽  
Author(s):  
Bo-Shen Gong ◽  
Rui Wang ◽  
Hong-Xia Xu ◽  
Ming-Yong Miao ◽  
Zhen-Zhen Yao

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.


Author(s):  
Rolando F. Del Maestro ◽  
Joseph F. Megyesi ◽  
Catherine L. Farrell

ABSTRACT:An understanding of the mechanisms responsible for tumor-associated edema involves the elucidation of the role played by a number of intra-related processes. These include (i) the permeability of new tumor microvessels that are associated with tumor angiogenesis; (ii) alterations in microvascular permeability due to factors secreted by tumor cells; (iii) immunological mechanisms and (iv) increased microvessel permeability associated with inflammation. The rationale for a role for inflammatory processes in tumor-associated edema has been outlined and the role of non-steroidal anti-inflammatory drugs in modulating experimental and human tumor-associated edema has been explored.


Blood ◽  
2009 ◽  
Vol 113 (14) ◽  
pp. 3139-3146 ◽  
Author(s):  
Thorsten Hagemann ◽  
Subhra K. Biswas ◽  
Toby Lawrence ◽  
Antonio Sica ◽  
Claire E. Lewis

Abstract The pivotal role of tumor-associated macrophages (TAMs) in tumor progression is now well established. TAMs have been shown to influence multiple steps in tumor development including the growth, survival, invasion, and metastasis of tumor cells as well as angiogenesis and lymphangiogenesis in tumors. The molecular circuits that polarize TAMs toward such a protumoral phenotype are now the focus of intense investigation. The transcription factor, nuclear factor–κB (NF-κB), is a master regulator of many cellular processes and been shown to regulate various pathways that impact on the function of TAMs. Much evidence for this has come from the use of elegant transgenic murine tumor models in which modification of single components of the NF-κB signaling pathway has been shown to regulate the pro-tumor repertoire of TAMs. Here, we outline this evidence and attempt to reconcile the various views that have emerged recently over the exact role of NF-κB in this phenomenon.


2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Birgit Mosch ◽  
Bettina Reissenweber ◽  
Christin Neuber ◽  
Jens Pietzsch

Eph receptors and their ephrin ligands were identified in the late 1980's. Subsequently, they were linked to different physiological and pathophysiological processes like embryonic development, angiogenesis, and tumorigenesis. In this regard, recent work focused on the distribution and effects of Eph receptors and ephrins on tumor cells and tumor microenvironment. The purpose of this review is to outline the role of these molecules in physiological angiogenesis and pathophysiological tumor angiogenesis. Furthermore, novel therapeutical approaches are discussed as Eph receptors and ephrins represent attractive targets for antiangiogenic therapy.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3162
Author(s):  
Stephan J. Reshkin ◽  
Rosa Angela Cardone

While research previously focused extensively on the tumor cells, over the last two decades, the tumor microenvironment (TME) has received increasing attention with a particular emphasis in its role in tumor development, metabolism, progression, and treatment response [...]


2018 ◽  
Vol 21 (2) ◽  
pp. 68-71
Author(s):  
O. N Sergeeva ◽  
N. V Palkina ◽  
M. B Aksenenko ◽  
A. V Komina ◽  
E. Yu Sergeeva ◽  
...  

Tumor microenvironment is known to be an active participant of tumor development. Tumor microenvironment is functional cell community interacting with cancer cells and promoting proliferation, invasion and metastasis of tumor cells. In the article features of Ki-67 and NFE2L2 expression levels in target organs of melanoma metastasis in premetastatic phase are investigated. Increased Ki-67expression levels in lung tissue, liver and kidneys and decreased NFE2L2 levels in liverandkidneys can be the markers of structural and functional reorganization of melanoma metastasis target organs in premetastatic phase of melanoma development.


2020 ◽  
Vol 15 (7) ◽  
pp. 607-613 ◽  
Author(s):  
Haiping Liu ◽  
Yiqian Liu ◽  
Xiaochuan Zhang ◽  
Xiaodong Wang

Gastric cancer (GC) is the fourth-most common cancer in the world, with an estimated 1.034 million new cases in 2015, and the third-highest cause of cancer deaths, estimated at 785,558, in 2014. Early diagnosis and treatment greatly affect the survival rate in patients with GC: the 5‐year survival rate of early GC reaches 90%‐95%, while the mortality rate significantly increases if GC develops to the late stage. Recently, studies for the role of RhoA in the diseases have become a hot topic, especially in the development of tumors. A study found that RhoA can regulate actin polymerization, cell adhesion, motor-myosin, cell transformation, and the ability to participate in the activities of cell movement, proliferation, migration, which are closely related to the invasion and metastasis of tumor cells. However, the specific role of RhoA in tumor cells remains to be studied. Therefore, our current study aimed to briefly review the role of RhoA in GC, especially for its associated signaling pathways involved in the GC progression.


2010 ◽  
Vol 10 ◽  
pp. 2367-2384 ◽  
Author(s):  
Eduardo Pérez-Gómez ◽  
Gaelle del Castillo ◽  
Juan Francisco Santibáñez ◽  
Jose Miguel Lêpez-Novoa ◽  
Carmelo Bernabéu ◽  
...  

Endoglin (CD105) is an auxiliary membrane receptor of transforming growth factor beta (TGF-β) that interacts with type I and type II TGF-β receptors and modulates TGF-β signaling. Endoglin is overexpressed in the tumor-associated vascular endothelium, where it modulates angiogenesis. This feature makes endoglin a promising target for antiangiogenic cancer therapy. In addition, recent studies on human and experimental models of carcinogenesis point to an important tumor cell–autonomous role of endoglin by regulating proliferation, migration, invasion, and metastasis. These studies suggest that endoglin behaves as a suppressor of malignancy in experimental and human epithelial carcinogenesis, although it can also promote metastasis in other types of cancer. In this review, we evaluate the implication of endoglin in tumor development underlying studies developed in our laboratories in recent years.


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