The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
John Laterra - One of the best experts on this subject based on the ideXlab platform.
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Tumor Microenvironment tenascin c promotes glioblastoma invasion and negatively regulates Tumor proliferation
Neuro-oncology, 2016Co-Authors: Brian Tung, Shervin Wang, Rory C Goodwin, John LaterraAbstract:Abstract Glioblastoma (GBM) is the most frequent and aggressive primary brain Tumor in adults. Recent research on cancer stroma indicates that the brain Microenvironment plays a substantial role in Tumor malignancy and treatment responses to current antiTumor therapy. In this work, we have investigated the effect of alterations in brain Tumor extracellular matrix tenascin-C (TNC) on brain Tumor growth patterns including proliferation and invasion. Since intracranial xenografts from patient-derived GBM neurospheres form highly invasive Tumors that recapitulate the invasive features demonstrated in human patients diagnosed with GBM, we studied TNC gain-of-function and loss-of function in these GBM neurospheres in vitro and in vivo. TNC loss-of-function promoted GBM neurosphere cell adhesion and actin cytoskeleton organization. Yet, TNC loss-of-function or exogenous TNC had no effect on GBM neurosphere cell growth in vitro. In animal models, decreased TNC in the Tumor Microenvironment was accompanied by decreased Tumor invasion and increased Tumor proliferation, suggesting that TNC regulates the "go-or-grow" phenotypic switch of glioma in vivo. We demonstrated that decreased TNC in the Tumor Microenvironment modulated behaviors of stromal cells including endothelial cells and microglia, resulting in enlarged Tumor blood vessels and activated microglia in Tumors. We further demonstrated that Tumor cells with decreased TNC expression are sensitive to anti-proliferative treatment in vitro. Our findings suggest that detailed understanding of how TNC in the Tumor Microenvironment influences Tumor behavior and the interactions between Tumor cells and surrounding nonTumor cells will benefit novel combinatory antiTumor strategies to treat malignant brain Tumors.
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Tumor Microenvironment tenascin c promotes glioblastoma invasion and negatively regulates Tumor proliferation
Neuro-oncology, 2016Co-Authors: Shuli Xia, Shervin Wang, Rory C Goodwin, Brian Tung, Bachchu Lal, John LaterraAbstract:BACKGROUND Glioblastoma (GBM) is the most frequent and aggressive primary brain Tumor in adults. Recent research on cancer stroma indicates that the brain Microenvironment plays a substantial role in Tumor malignancy and treatment responses to current antiTumor therapy. In this work, we have investigated the effect of alterations in brain Tumor extracellular matrix tenascin-C (TNC) on brain Tumor growth patterns including proliferation and invasion. METHODS Since intracranial xenografts from patient-derived GBM neurospheres form highly invasive Tumors that recapitulate the invasive features demonstrated in human patients diagnosed with GBM, we studied TNC gain-of-function and loss-of function in these GBM neurospheres in vitro and in vivo. RESULTS TNC loss-of-function promoted GBM neurosphere cell adhesion and actin cytoskeleton organization. Yet, TNC loss-of-function or exogenous TNC had no effect on GBM neurosphere cell growth in vitro. In animal models, decreased TNC in the Tumor Microenvironment was accompanied by decreased Tumor invasion and increased Tumor proliferation, suggesting that TNC regulates the "go-or-grow" phenotypic switch of glioma in vivo. We demonstrated that decreased TNC in the Tumor Microenvironment modulated behaviors of stromal cells including endothelial cells and microglia, resulting in enlarged Tumor blood vessels and activated microglia in Tumors. We further demonstrated that Tumor cells with decreased TNC expression are sensitive to anti-proliferative treatment in vitro. CONCLUSION Our findings suggest that detailed understanding of how TNC in the Tumor Microenvironment influences Tumor behavior and the interactions between Tumor cells and surrounding nonTumor cells will benefit novel combinatory antiTumor strategies to treat malignant brain Tumors.
Daniel Olive - One of the best experts on this subject based on the ideXlab platform.
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Endometrial Tumor Microenvironment Alters Human NK Cell Recruitment, and Resident NK Cell Phenotype and Function
Frontiers in Immunology, 2019Co-Authors: Clara Degos, Mellie Heinemann, Julien Barrou, Nicolas Boucherit, Eric Lambaudie, Ariel Savina, Laurent Gorvel, Daniel OliveAbstract:Endometrial Cancer is the most common cancer in the female genital tract in developed countries, and with its increasing incidence due to risk factors such as aging and obesity tends to become a public health issue. However, its immune environment has been less characterized than in other Tumors such as breast cancers. NK cells are cytotoxic innate lymphoid cells that are considered as a major anti-Tumoral effector cell type which function is drastically altered in Tumors which participates to Tumor progression. Here we characterize Tumor NK cells both phenotypically and functionally in the Tumor Microenvironment of endometrial cancer. For that, we gathered endometrial Tumors, Tumor adjacent healthy tissue, blood from matching patients and healthy donor blood to perform comparative analysis of NK cells. First we found that NK cells were impoverished in the Tumor infiltrate. We then compared the phenotype of NK cells in the Tumor and found that Tumor resident CD103+ NK cells exhibited more co-inhibitory molecules such as Tigit, and TIM-3 compared to recruited CD103- NK cells and that the expression of these molecules increased with the severity of the disease. We showed that both chemokines (CXCL12, IP-10, and CCL27) and cytokines profiles (IL-1β and IL-6) were altered in the Tumor Microenvironment and might reduce NK cell function and recruitment to the Tumor site. This led to hypothesize that the Tumor Microenvironment reduces resident NK cells cytotoxicity which we confirmed by measuring cytotoxic effector production and degranulation. Taken together, our results show that the Tumor Microenvironment reshapes NK cell phenotype and function to promote Tumor progression.
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Image_1_Endometrial Tumor Microenvironment Alters Human NK Cell Recruitment, and Resident NK Cell Phenotype and Function.TIF
2019Co-Authors: Clara Degos, Mellie Heinemann, Julien Barrou, Nicolas Boucherit, Eric Lambaudie, Ariel Savina, Laurent Gorvel, Daniel OliveAbstract:Endometrial Cancer is the most common cancer in the female genital tract in developed countries, and with its increasing incidence due to risk factors such as aging and obesity tends to become a public health issue. However, its immune environment has been less characterized than in other Tumors such as breast cancers. NK cells are cytotoxic innate lymphoid cells that are considered as a major anti-Tumoral effector cell type which function is drastically altered in Tumors which participates to Tumor progression. Here we characterize Tumor NK cells both phenotypically and functionally in the Tumor Microenvironment of endometrial cancer. For that, we gathered endometrial Tumors, Tumor adjacent healthy tissue, blood from matching patients and healthy donor blood to perform comparative analysis of NK cells. First we found that NK cells were impoverished in the Tumor infiltrate. We then compared the phenotype of NK cells in the Tumor and found that Tumor resident CD103+ NK cells exhibited more co-inhibitory molecules such as Tigit, and TIM-3 compared to recruited CD103− NK cells and that the expression of these molecules increased with the severity of the disease. We showed that both chemokines (CXCL12, IP-10, and CCL27) and cytokines profiles (IL-1β and IL-6) were altered in the Tumor Microenvironment and might reduce NK cell function and recruitment to the Tumor site. This led to hypothesize that the Tumor Microenvironment reduces resident NK cells cytotoxicity which we confirmed by measuring cytotoxic effector production and degranulation. Taken together, our results show that the Tumor Microenvironment reshapes NK cell phenotype and function to promote Tumor progression.
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Table_1_Endometrial Tumor Microenvironment Alters Human NK Cell Recruitment, and Resident NK Cell Phenotype and Function.xlsx
2019Co-Authors: Clara Degos, Mellie Heinemann, Julien Barrou, Nicolas Boucherit, Eric Lambaudie, Ariel Savina, Laurent Gorvel, Daniel OliveAbstract:Endometrial Cancer is the most common cancer in the female genital tract in developed countries, and with its increasing incidence due to risk factors such as aging and obesity tends to become a public health issue. However, its immune environment has been less characterized than in other Tumors such as breast cancers. NK cells are cytotoxic innate lymphoid cells that are considered as a major anti-Tumoral effector cell type which function is drastically altered in Tumors which participates to Tumor progression. Here we characterize Tumor NK cells both phenotypically and functionally in the Tumor Microenvironment of endometrial cancer. For that, we gathered endometrial Tumors, Tumor adjacent healthy tissue, blood from matching patients and healthy donor blood to perform comparative analysis of NK cells. First we found that NK cells were impoverished in the Tumor infiltrate. We then compared the phenotype of NK cells in the Tumor and found that Tumor resident CD103+ NK cells exhibited more co-inhibitory molecules such as Tigit, and TIM-3 compared to recruited CD103− NK cells and that the expression of these molecules increased with the severity of the disease. We showed that both chemokines (CXCL12, IP-10, and CCL27) and cytokines profiles (IL-1β and IL-6) were altered in the Tumor Microenvironment and might reduce NK cell function and recruitment to the Tumor site. This led to hypothesize that the Tumor Microenvironment reduces resident NK cells cytotoxicity which we confirmed by measuring cytotoxic effector production and degranulation. Taken together, our results show that the Tumor Microenvironment reshapes NK cell phenotype and function to promote Tumor progression.
Yuval Shaked - One of the best experts on this subject based on the ideXlab platform.
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analysis of the stromal cellular components of the solid Tumor Microenvironment using flow cytometry
Current protocols in pharmacology, 2016Co-Authors: Michael Timaner, Ofrat Beyarkatz, Yuval ShakedAbstract:The Tumor Microenvironment consists of a variety of cell types. The contribution of each cell type to the Tumor is an emerging subject in the field of cancer research. Here, we describe protocols for dissociating Tumor tissues and Matrigel plugs into single cells for further analysis by flow cytometry. These protocols can be used for evaluating the cellular component of solid Tumors from human or mouse origin or Matrigel plugs implanted in mice. The protocols describe the dissociation of Tumor tissue with or without dissociation automatic devices. Subsequently, the use of flow cytometry for immunophenotypic analysis of host cells found in the Tumor Microenvironment, including myeloid derived suppressor cells, endothelial cells, and macrophages is provided. These methods can be used to broaden our understanding of the cross-talk between Tumor and host cells in the Tumor Microenvironment. © 2016 by John Wiley & Sons, Inc.
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analysis of the stromal cellular components of the solid Tumor Microenvironment using flow cytometry
Current protocols in pharmacology, 2016Co-Authors: Michael Timaner, Ofrat Beyarkatz, Yuval ShakedAbstract:The Tumor Microenvironment consists of a variety of cell types. The contribution of each cell type to the Tumor is an emerging subject in the field of cancer research. Here, we describe protocols for dissociating Tumor tissues and Matrigel plugs into single cells for further analysis by flow cytometry. These protocols can be used for evaluating the cellular component of solid Tumors from human or mouse origin or Matrigel plugs implanted in mice. The protocols describe the dissociation of Tumor tissue with or without dissociation automatic devices. Subsequently, the use of flow cytometry for immunophenotypic analysis of host cells found in the Tumor Microenvironment, including myeloid derived suppressor cells, endothelial cells, and macrophages is provided. These methods can be used to broaden our understanding of the cross-talk between Tumor and host cells in the Tumor Microenvironment. © 2016 by John Wiley & Sons, Inc. Keywords: bone marrow derived cells; host; cancer cells; cell dissociation
Amato J Giaccia - One of the best experts on this subject based on the ideXlab platform.
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Tumor Microenvironment and cellular stress signaling metabolism imaging and therapeutic targets preface
Advances in Experimental Medicine and Biology, 2014Co-Authors: Constantinos Koumenis, Ester M Hammond, Amato J GiacciaAbstract:Introduction.- Hypoxia and metabolism in cancer.- Hypoxia and Regulation of Cancer Cell Stemness.- Hypoxia-mediated metastasis.- Escape Mechanisms from Antiangiogenic Therapy: An Immune Cell's Perspective.- Hypoxic VDAC1: a potential mitochondrial marker for cancer therapy.- Hypoxia directed drug strategies to target the Tumor Microenvironment.- Radiotherapy and the Tumor Microenvironment: Mutual Influence and Clinical Implications.- Autophagy and cell death to target cancer cells: exploiting synthetic lethality as cancer therapeutic.- IntraTumoral Hypoxia as the Genesis of Genetic Instability and Clinical Prognosis in Prostate Cancer.- miR-210: Fine-Tuning the Hypoxic Response.- The role of complement in Tumor growth.- Imaging angiogenesis, inflammation and metastasis in the Tumor Microenvironment with magnetic resonance imaging.- Index.
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hypoxia inflammation and the Tumor Microenvironment in metastatic disease
Cancer and Metastasis Reviews, 2010Co-Authors: Elizabeth C Finger, Amato J GiacciaAbstract:Metastasis, the leading cause of cancer deaths, is an intricate process involving many important Tumor and stromal proteins that have yet to be fully defined. This review discusses critical components necessary for the metastatic cascade, including hypoxia, inflammation, and the Tumor Microenvironment. More specifically, this review focuses on Tumor cell and stroma interactions, which allow cell detachment from a primary Tumor, intravasation to the blood stream, and extravasation at a distant site where cells can seed and Tumor metastases can form. Central players involved in this process and discussed in this review include integrins, matrix metalloproteinases, and soluble growth factors/matrix proteins, including the connective tissue growth factor and lysyl oxidase.
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anaerobic bacteria as a gene delivery system that is controlled by the Tumor Microenvironment
Gene Therapy, 1997Co-Authors: Marilyn J. Lemmon, Pierre Van Zijl, Margaret Lamble Mauchline, Nigel P Minton, Amato J Giaccia, J M BrownAbstract:Anaerobic bacteria as a gene delivery system that is controlled by the Tumor Microenvironment
Brian Tung - One of the best experts on this subject based on the ideXlab platform.
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Tumor Microenvironment tenascin c promotes glioblastoma invasion and negatively regulates Tumor proliferation
Neuro-oncology, 2016Co-Authors: Brian Tung, Shervin Wang, Rory C Goodwin, John LaterraAbstract:Abstract Glioblastoma (GBM) is the most frequent and aggressive primary brain Tumor in adults. Recent research on cancer stroma indicates that the brain Microenvironment plays a substantial role in Tumor malignancy and treatment responses to current antiTumor therapy. In this work, we have investigated the effect of alterations in brain Tumor extracellular matrix tenascin-C (TNC) on brain Tumor growth patterns including proliferation and invasion. Since intracranial xenografts from patient-derived GBM neurospheres form highly invasive Tumors that recapitulate the invasive features demonstrated in human patients diagnosed with GBM, we studied TNC gain-of-function and loss-of function in these GBM neurospheres in vitro and in vivo. TNC loss-of-function promoted GBM neurosphere cell adhesion and actin cytoskeleton organization. Yet, TNC loss-of-function or exogenous TNC had no effect on GBM neurosphere cell growth in vitro. In animal models, decreased TNC in the Tumor Microenvironment was accompanied by decreased Tumor invasion and increased Tumor proliferation, suggesting that TNC regulates the "go-or-grow" phenotypic switch of glioma in vivo. We demonstrated that decreased TNC in the Tumor Microenvironment modulated behaviors of stromal cells including endothelial cells and microglia, resulting in enlarged Tumor blood vessels and activated microglia in Tumors. We further demonstrated that Tumor cells with decreased TNC expression are sensitive to anti-proliferative treatment in vitro. Our findings suggest that detailed understanding of how TNC in the Tumor Microenvironment influences Tumor behavior and the interactions between Tumor cells and surrounding nonTumor cells will benefit novel combinatory antiTumor strategies to treat malignant brain Tumors.
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Tumor Microenvironment tenascin c promotes glioblastoma invasion and negatively regulates Tumor proliferation
Neuro-oncology, 2016Co-Authors: Shuli Xia, Shervin Wang, Rory C Goodwin, Brian Tung, Bachchu Lal, John LaterraAbstract:BACKGROUND Glioblastoma (GBM) is the most frequent and aggressive primary brain Tumor in adults. Recent research on cancer stroma indicates that the brain Microenvironment plays a substantial role in Tumor malignancy and treatment responses to current antiTumor therapy. In this work, we have investigated the effect of alterations in brain Tumor extracellular matrix tenascin-C (TNC) on brain Tumor growth patterns including proliferation and invasion. METHODS Since intracranial xenografts from patient-derived GBM neurospheres form highly invasive Tumors that recapitulate the invasive features demonstrated in human patients diagnosed with GBM, we studied TNC gain-of-function and loss-of function in these GBM neurospheres in vitro and in vivo. RESULTS TNC loss-of-function promoted GBM neurosphere cell adhesion and actin cytoskeleton organization. Yet, TNC loss-of-function or exogenous TNC had no effect on GBM neurosphere cell growth in vitro. In animal models, decreased TNC in the Tumor Microenvironment was accompanied by decreased Tumor invasion and increased Tumor proliferation, suggesting that TNC regulates the "go-or-grow" phenotypic switch of glioma in vivo. We demonstrated that decreased TNC in the Tumor Microenvironment modulated behaviors of stromal cells including endothelial cells and microglia, resulting in enlarged Tumor blood vessels and activated microglia in Tumors. We further demonstrated that Tumor cells with decreased TNC expression are sensitive to anti-proliferative treatment in vitro. CONCLUSION Our findings suggest that detailed understanding of how TNC in the Tumor Microenvironment influences Tumor behavior and the interactions between Tumor cells and surrounding nonTumor cells will benefit novel combinatory antiTumor strategies to treat malignant brain Tumors.
