scholarly journals Eph Receptors and Ephrin Ligands: Important Players in Angiogenesis and Tumor Angiogenesis

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Birgit Mosch ◽  
Bettina Reissenweber ◽  
Christin Neuber ◽  
Jens Pietzsch
Keyword(s):  
Tumor Microenvironment ◽  
Embryonic Development ◽  
Tumor Cells ◽  
Recent Work ◽  
Tumor Angiogenesis ◽  
Antiangiogenic Therapy ◽  
Eph Receptors ◽  
Ephrin Ligands

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.

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.

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 RAC1 Takes the Lead in Solid Tumors

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 382 ◽  
Author(s):  
Pradip De ◽  
Jennifer Carlson Aske ◽  
Nandini Dey
Keyword(s):  
Drug Resistance ◽  
Embryonic Development ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Cellular Localization ◽  
Regulatory Mechanisms ◽  
Cellular Functions ◽  
Patterns Of Distribution ◽  
Background Data

Three GTPases, RAC, RHO, and Cdc42, play essential roles in coordinating many cellular functions during embryonic development, both in healthy cells and in disease conditions like cancers. We have presented patterns of distribution of the frequency of RAC1-alteration(s) in cancers as obtained from cBioPortal. With this background data, we have interrogated the various functions of RAC1 in tumors, including proliferation, metastasis-associated phenotypes, and drug-resistance with a special emphasis on solid tumors in adults. We have reviewed the activation and regulation of RAC1 functions on the basis of its sub-cellular localization in tumor cells. Our review focuses on the role of RAC1 in cancers and summarizes the regulatory mechanisms, inhibitory efficacy, and the anticancer potential of RAC1-PAK targeting agents.

scholarly journals Inflammatory Cells in Diffuse Large B Cell Lymphoma

2020 ◽  
Vol 9 (8) ◽  
pp. 2418
Author(s):  
Roberto Tamma ◽  
Girolamo Ranieri ◽  
Giuseppe Ingravallo ◽  
Tiziana Annese ◽  
Angela Oranger ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B cell lymphoma (DLBCL), known as the most common non-Hodgkin lymphoma (NHL) subtype, is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME), in which the tumor cells reside, is crucial in the regulation of tumor initiation, progression, and metastasis, but it also has profound effects on therapeutic efficacy. The role of immune cells during DLBCL development is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators and structural components present in the tumor microenvironment. Different immune cells are recruited into the tumor microenvironment and exert distinct effects on tumor progression and therapeutic outcomes. In this review, we focused on the role of macrophages, Neutrophils, T cells, natural killer cells and dendritic cells in the DLBCL microenvironment and their implication as target for DLBCL treatment. These new therapies, carried out by the induction of adaptive immunity through vaccination or passive of immunologic effectors delivery, enhance the ability of the immune system to react against the tumor antigens inducing the destruction of tumor cells.

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 The Role of Extracellular Vesicles in Cancer: Cargo, Function, and Therapeutic Implications

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 93 ◽  
Author(s):  
James Jabalee ◽  
Rebecca Towle ◽  
Cathie Garnis
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Tumor Stroma ◽  
Therapeutic Implications ◽  
Membrane Bound ◽  
Immune Destruction ◽  
And Function ◽  
Cargo Molecule

Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound structures that play key roles in intercellular communication. EVs are potent regulators of tumorigenesis and function largely via the shuttling of cargo molecules (RNA, DNA, protein, etc.) among cancer cells and the cells of the tumor stroma. EV-based crosstalk can promote proliferation, shape the tumor microenvironment, enhance metastasis, and allow tumor cells to evade immune destruction. In many cases these functions have been linked to the presence of specific cargo molecules. Herein we will review various types of EV cargo molecule and their functional impacts in the context of oncology.

scholarly journals TAMI-02. ALTERATIONS IN C-X3-C MOTIF CHEMOKINE RECEPTOR 1 (CX3CR1) EXPRESSION INFLUENCE MICROGLIAL AND MACROPHAGE RESPONSE IN DIFFERENT STEPS OF CEREBRAL METASTASIS FORMATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii213-ii213
Author(s):  
Wenlong Zhang ◽  
Iven-Alex von Mücke-Heim ◽  
Matthias Mulazzani ◽  
Philipp Karschnia ◽  
Andreas Straube ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Laser Scanning Microscopy ◽  
Cerebral Metastasis ◽  
Body Volume ◽  
Metastasis Formation ◽  
Cranial Window ◽  
Deficient Mice

Abstract Metastasis to the brain is a frequent complication in lung cancer and is still associated with a dismal prognosis. Current treatment strategies not only target tumor cells but also focus on cells of the tumor microenvironment like tumor associated microglia/macrophages (TAMs). The interactions between tumor cells and TAMs during different steps of cerebral metastasis formation of lung cancer brain metastasis are poorly characterized. Moreover, the role of CX3CR1 in this process remains unclear. We established a syngeneic cerebral metastasis mouse model by combining a chronic cranial window and two-photon laser scanning microscopy (TPLSM), which allows the tracking of single fluorescent metastasizing tumor cells and the tumor microenvironment on a cellular resolution in vivoover time for a period of weeks. Transgenic CX3CR1 proficient and deficient mice (CX3CRGFP/wt and CX3CR1GFP/GFP) were injected with red fluorescent Lewis lung carcinoma cells. During different steps of metastasis formation (extravasation, formation of micro- and macrometastasis) the density and cell body volume of TAMs, their interaction with tumor cells and possible influence on the fate of single metastatic tumor cells were investigated using serial TPLSM. We found that during metastasis formation TAM density was significantly lower in CX3CR1 deficient mice. However, activation as assessed by TAM morphology did not differ in the absence of CX3CR1. Strikingly, CX3CR1 deficiency was associated with a significant increase of tumor cells successfully extravasating the cerebral vasculature. However, subsequent steps (mirco- and macrometastasis formation) were observed less frequent in CX3CR1 deficient mice. In summary, our results highlight a complex role of CX3CR1 for TAMs during cerebral metastasis formation, indicating anti-tumorous properties of CX3CR1 at early steps and possible pro-tumorous effects at later stages (micro- and macrometastasis formation).

scholarly journals Rho–ROCK signaling regulates tumor-microenvironment interactions

2018 ◽  
Vol 47 (1) ◽  
pp. 101-108 ◽  
Author(s):  
Mohammad Zahied Johan ◽  
Michael S. Samuel
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Migration And Invasion ◽  
Cellular Functions ◽  
Cancer Cell Growth ◽  
Current State ◽  
Clinical Models ◽  
Endothelial Migration ◽  
Biophysical Interactions

Abstract Reciprocal biochemical and biophysical interactions between tumor cells, stromal cells and the extracellular matrix (ECM) result in a unique tumor microenvironment that determines disease outcome. The cellular component of the tumor microenvironment contributes to tumor growth by providing nutrients, assisting in the infiltration of immune cells and regulating the production and remodeling of the ECM. The ECM is a noncellular component of the tumor microenvironment and provides both physical and biochemical support to the tumor cells. Rho–ROCK signaling is a key regulator of actomyosin contractility and regulates cell shape, cytoskeletal arrangement and thereby cellular functions such as cell proliferation, differentiation, motility and adhesion. Rho–ROCK signaling has been shown to promote cancer cell growth, migration and invasion. However, it is becoming clear that this pathway also regulates key tumor-promoting properties of the cellular and noncellular components of the tumor microenvironment. There is accumulating evidence that Rho–ROCK signaling enhances ECM stiffness, modifies ECM composition, increases the motility of tumor-associated fibroblasts and lymphocytes and promotes trans-endothelial migration of tumor-associated lymphocytes. In this review, we briefly discuss the current state of knowledge on the role of Rho–ROCK signaling in regulating the tumor microenvironment and the implications of this knowledge for therapy, potentially via the development of selective inhibitors of the components of this pathway to permit the tuning of signaling flux, including one example with demonstrated utility in pre-clinical models.

scholarly journals Myeloid Cells in the Tumor Microenvironment: Modulation of Tumor Angiogenesis and Tumor Inflammation

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Michael C. Schmid ◽  
Judith A. Varner
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Angiogenesis ◽  
Malignant Tumors ◽  
Critical Role ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Promote Tumor Growth ◽  
Bone Marrow Derived Cells

Myeloid cells are a heterogeneous population of bone marrow-derived cells that play a critical role during growth and metastasis of malignant tumors. Tumors exhibit significant myeloid cell infiltrates, which are actively recruited to the tumor microenvironment. Myeloid cells promote tumor growth by stimulating tumor angiogenesis, suppressing tumor immunity, and promoting metastasis to distinct sites. In this review, we discuss the role of myeloid cells in promoting tumor angiogenesis. Furthermore, we describe a subset of myeloid cells with immunosuppressive activity (known as myeloid-derived suppressor cells). Finally, we will comment on the mechanisms regulating myeloid cell recruitment to the tumor microenvironment and on the potential of myeloid cells as new targets for cancer therapy.

scholarly journals Obesity and Cancer Metastasis: Molecular and Translational Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3798
Author(s):  
Stephanie Annett ◽  
Gillian Moore ◽  
Tracy Robson
Keyword(s):  
Adipose Tissue ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Metastatic Tumor ◽  
Established Risk Factor ◽  
Metastatic Behavior ◽  
Obesity And Cancer ◽  
Enhance Tumor Growth

Obesity is a modern health problem that has reached pandemic proportions. It is an established risk factor for carcinogenesis, however, evidence for the contribution of adipose tissue to the metastatic behavior of tumors is also mounting. Over 90% of cancer mortality is attributed to metastasis and metastatic tumor cells must communicate with their microenvironment for survival. Many of the characteristics observed in obese adipose tissue strongly mirror the tumor microenvironment. Thus in the case of prostate, pancreatic and breast cancer and esophageal adenocarcinoma, which are all located in close anatomical proximity to an adipose tissue depot, the adjacent fat provides an ideal microenvironment to enhance tumor growth, progression and metastasis. Adipocytes provide adipokines, fatty acids and other soluble factors to tumor cells whilst immune cells infiltrate the tumor microenvironment. In addition, there are emerging studies on the role of the extracellular vesicles secreted from adipose tissue, and the extracellular matrix itself, as drivers of obesity-induced metastasis. In the present review, we discuss the major mechanisms responsible for the obesity–metastatic link. Furthermore, understanding these complex mechanisms will provide novel therapies to halt the tumor–adipose tissue crosstalk with the ultimate aim of inhibiting tumor progression and metastatic growth.

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