The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Julia Frose - One of the best experts on this subject based on the ideXlab platform.
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a breast cancer stem cell niche supported by Juxtacrine Signalling from monocytes and macrophages
Nature Cell Biology, 2014Co-Authors: Haihui Lu, Karl R Clauser, Julia Frose, Xin Ye, Elinor Ng Eaton, Ferenc Reinhardt, Vera S Donnenberg, Rohit BhargavaAbstract:Weinberg and colleagues report that monocytes and macrophages interact with stem-like human mammary epithelial cells to create a breast cancer stem cell niche.
Rohit Bhargava - One of the best experts on this subject based on the ideXlab platform.
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Abstract B150: Juxtacrine signaling between the tumor-associated macrophages and the breast cancer stem cells contribute to the cancer stem cell niche by inducing a cytokine signaling network
Cancer immunology research, 2016Co-Authors: Haihui Lu, Xin Ye, Vera S Donnenberg, Rohit Bhargava, Robert A. WeinbergAbstract:The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. In addition, EMT upregulates the expression of cell surface receptors that enable CSCs to interact with their surrounding microenvironment in order to sustain their stem cell state. We discovered that EphA4 and CD90, two cell surface proteins upregulated in the carcinoma cells by the EMT, mediate Juxtacrine Signalling between the CSCs and tumor-associated monocytes and macrophages (TAMs). When engaged with its counter-receptor on TAMs, EphA4 on the CSCs activates Src and PLCγ1, the latter resulting in the translocation of NF-κB into the nucleus, which cooperates with Twist to drive the rapid induction of a variety of cytokines in the CSCs. Among the secreted cytokines IL-8 and IL-6 maintain the CSC-state by reinforcing the expression of the EMT-inducing transcription factors, whereas other cytokines GM-CSF, M-CSF and IL-10 recruit monocytes and induce their differentiation into M2-like macrophages. Together these cytokines perpetuate the CSC-promoting interactions between CSCs and TAMs. Indeed, admixed TAMs promote the tumor-initiating ability of CSCs whereas ablation of endogenous macrophages substantially diminished tumor initiation. Importantly, the juxtaposition of TAMs with the mesenchymal-like CD90high CSCs can be observed at the invading edge in primary human breast tumor sections and xenograft tumors. On the contrary, we rarely find TAMS infiltrating beyond the edge of tumors into the regions where the CD90neg non-stem carcinoma cells reside. These findings underscore the importance of TAMs as critical components of the CSC niche and highlight their potential as therapeutics targets. Citation Format: Haihui Lu, Wai Leong Tam, Vera Donnenberg, Xin Ye, Rohit Bhargava, Robert Weinberg. Juxtacrine signaling between the tumor-associated macrophages and the breast cancer stem cells contribute to the cancer stem cell niche by inducing a cytokine signaling network. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B150.
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a breast cancer stem cell niche supported by Juxtacrine Signalling from monocytes and macrophages
Nature Cell Biology, 2014Co-Authors: Haihui Lu, Karl R Clauser, Julia Frose, Xin Ye, Elinor Ng Eaton, Ferenc Reinhardt, Vera S Donnenberg, Rohit BhargavaAbstract:Weinberg and colleagues report that monocytes and macrophages interact with stem-like human mammary epithelial cells to create a breast cancer stem cell niche.
Nicholas A.m. Monk - One of the best experts on this subject based on the ideXlab platform.
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Effect of time delay on pattern formation : Competition between homogenisation and patterning
Physica D: Nonlinear Phenomena, 2005Co-Authors: Siren R. Veflingstad, Erik Plahte, Nicholas A.m. MonkAbstract:Abstract We study a mathematical model for Juxtacrine Signalling in a discrete lattice of cells. As the Signalling is assumed to be under transcriptional control, and transcription is a time-consuming process, we incorporate time delays in the equations and study the effect of this on the pattern forming potential of the model. Previous models without time delays have shown that the mechanism is able to generate spatial patterns. The analysis of the delay-model reveals a transient competition between patterning and homogeneous oscillations. A fine-grained pattern eventually appears over the whole lattice, but the duration of the oscillatory behaviour increases as the time delay increases. The results illustrate the importance of including the known delays in a model and of studying transients, as these may not be favourable to the system. In addition, the results may suggest that there are other mechanisms regulating the Signalling than transcription, for example protein–protein interactions, which would render the patterning process much faster.
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Effect of time delay on pattern formation: Competition between homogenisation and patterning
Physica D: Nonlinear Phenomena, 2005Co-Authors: Siren R. Veflingstad, Erik Plahte, Nicholas A.m. MonkAbstract:We study a mathematical model for Juxtacrine Signalling in a discrete lattice of cells. As the Signalling is assumed to be under transcriptional control, and transcription is a time-consuming process, we incorporate time delays in the equations and study the effect of this on the pattern forming potential of the model. Previous models without time delays have shown that the mechanism is able to generate spatial patterns. The analysis of the delay-model reveals a transient competition between patterning and homogeneous oscillations. A fine-grained pattern eventually appears over the whole lattice, but the duration of the oscillatory behaviour increases as the time delay increases. The results illustrate the importance of including the known delays in a model and of studying transients, as these may not be favourable to the system. In addition, the results may suggest that there are other mechanisms regulating the Signalling than transcription, for example protein-protein interactions, which would render the patterning process much faster. © 2005 Elsevier B.V. All rights reserved.
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spatial patterning in explicitly cellular environments activity regulated Juxtacrine Signalling
2004Co-Authors: Nicholas A.m. MonkAbstract:Pattern formation in multicellular organisms generally occurs within populations of cells that are in close contact. It is thus natural and important to consider models of pattern formation that are constructed using a spatially discrete cellular structure. Here, the particular case of pattern formation in cellular systems that depends on contact-dependent Guxtacrine) Signalling between cells is dis cussed. Spatial and spatio-temporal patterns can emerge in populations of cells coupled by Juxtacrine Signalling when the degree of activation of the relevant cell surface receptors regulates both the pathway of differentiation adopted by the cell and the ability of the cell to participate in further Juxtacrine Signalling. When this latter condition applies, Juxtacrine Signalling couples alI the cells of a population to form a spatially extended Signalling network. Due to the essential nonlinearity of the Signalling, such Juxtacrine networks can exhibit dynarnics that are quite dif ferent to those in networks of cells coupled by linear diffusion. Two simple cases are discussed here, in which receptor activation either diminishes or enhances the Signalling ability of a cell. In the former case, Signalling can act to amplify small differences between cells via a feedback-mediated competition, leading to stable spatially periodic patterns (a process known as lateral inhibition). In the latter case, Signalling can result in a range of different patterns, including stable spatial gradients, propagating fronts, and periodic and quasi-periodic spatial patterns. These quite simple examples serve to illustrate the potential richness of this im portant class of biological Signalling, and provide guidance for the development of more complex models.
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spatiotemporal patterning in models of Juxtacrine intercellular Signalling with feedback
IMA, 2001Co-Authors: Nicholas A.m. Monk, Jonathan A Sherratt, Markus R OwenAbstract:Juxtacrine Signalling is the class of intercellular communication mediated by ligands and receptors that are both anchored in the cell membrane. Two particularly well documented examples of such Signalling pathways are the Delta-Notch and tgf α-egf-r interactions. In this review, we discuss mathematical models for Juxtacrine Signalling, focussing on these two specific examples. We discuss the various model formulations that have been used, and consider gradient, travelling front, and spatial pattern type solutions. We show that Juxtacrine mechanisms can explain a wide range of observed behaviours in each of these categories, in a manner that is genuinely different from that in traditional diffusion-based models for intercellular Signalling.
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Restricted-range gradients and travelling fronts in a model of Juxtacrine cell relay
Bulletin of Mathematical Biology, 1998Co-Authors: Nicholas A.m. MonkAbstract:Patterning events in development often depend on the transmission over a range of several cell diameters of signals emanating from a localized source. Experimental studies of such long-range Signalling by members of the TGF- β family of growth factors suggests that a cell-relay mechanism in which cells signal only with their immediate neighbours (i.e., Juxtacrine Signalling) may be operating in some tissues. Here, this possibility is investigated through the analysis of a model of Juxtacrine Signalling. Depending on the strength of the signal relay between cells, a localized signal source can generate either stable gradients or travelling fronts of cell activation. Both of these behaviors could in principle be involved in the long-range transmission of signals and patterning of cell fates by cell relays. There are significant and surprising differences between the gradients generated by the mechanism studied here, and those generated by the diffusion of a morphogen. In particular, there is an upper limit on the distance over which any given level of cell activation can be attained in a relay-mediated gradient, irrespective of the strength of signal source.
Haihui Lu - One of the best experts on this subject based on the ideXlab platform.
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Abstract B150: Juxtacrine signaling between the tumor-associated macrophages and the breast cancer stem cells contribute to the cancer stem cell niche by inducing a cytokine signaling network
Cancer immunology research, 2016Co-Authors: Haihui Lu, Xin Ye, Vera S Donnenberg, Rohit Bhargava, Robert A. WeinbergAbstract:The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. In addition, EMT upregulates the expression of cell surface receptors that enable CSCs to interact with their surrounding microenvironment in order to sustain their stem cell state. We discovered that EphA4 and CD90, two cell surface proteins upregulated in the carcinoma cells by the EMT, mediate Juxtacrine Signalling between the CSCs and tumor-associated monocytes and macrophages (TAMs). When engaged with its counter-receptor on TAMs, EphA4 on the CSCs activates Src and PLCγ1, the latter resulting in the translocation of NF-κB into the nucleus, which cooperates with Twist to drive the rapid induction of a variety of cytokines in the CSCs. Among the secreted cytokines IL-8 and IL-6 maintain the CSC-state by reinforcing the expression of the EMT-inducing transcription factors, whereas other cytokines GM-CSF, M-CSF and IL-10 recruit monocytes and induce their differentiation into M2-like macrophages. Together these cytokines perpetuate the CSC-promoting interactions between CSCs and TAMs. Indeed, admixed TAMs promote the tumor-initiating ability of CSCs whereas ablation of endogenous macrophages substantially diminished tumor initiation. Importantly, the juxtaposition of TAMs with the mesenchymal-like CD90high CSCs can be observed at the invading edge in primary human breast tumor sections and xenograft tumors. On the contrary, we rarely find TAMS infiltrating beyond the edge of tumors into the regions where the CD90neg non-stem carcinoma cells reside. These findings underscore the importance of TAMs as critical components of the CSC niche and highlight their potential as therapeutics targets. Citation Format: Haihui Lu, Wai Leong Tam, Vera Donnenberg, Xin Ye, Rohit Bhargava, Robert Weinberg. Juxtacrine signaling between the tumor-associated macrophages and the breast cancer stem cells contribute to the cancer stem cell niche by inducing a cytokine signaling network. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B150.
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a breast cancer stem cell niche supported by Juxtacrine Signalling from monocytes and macrophages
Nature Cell Biology, 2014Co-Authors: Haihui Lu, Karl R Clauser, Julia Frose, Xin Ye, Elinor Ng Eaton, Ferenc Reinhardt, Vera S Donnenberg, Rohit BhargavaAbstract:Weinberg and colleagues report that monocytes and macrophages interact with stem-like human mammary epithelial cells to create a breast cancer stem cell niche.
Vera S Donnenberg - One of the best experts on this subject based on the ideXlab platform.
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Abstract B150: Juxtacrine signaling between the tumor-associated macrophages and the breast cancer stem cells contribute to the cancer stem cell niche by inducing a cytokine signaling network
Cancer immunology research, 2016Co-Authors: Haihui Lu, Xin Ye, Vera S Donnenberg, Rohit Bhargava, Robert A. WeinbergAbstract:The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. In addition, EMT upregulates the expression of cell surface receptors that enable CSCs to interact with their surrounding microenvironment in order to sustain their stem cell state. We discovered that EphA4 and CD90, two cell surface proteins upregulated in the carcinoma cells by the EMT, mediate Juxtacrine Signalling between the CSCs and tumor-associated monocytes and macrophages (TAMs). When engaged with its counter-receptor on TAMs, EphA4 on the CSCs activates Src and PLCγ1, the latter resulting in the translocation of NF-κB into the nucleus, which cooperates with Twist to drive the rapid induction of a variety of cytokines in the CSCs. Among the secreted cytokines IL-8 and IL-6 maintain the CSC-state by reinforcing the expression of the EMT-inducing transcription factors, whereas other cytokines GM-CSF, M-CSF and IL-10 recruit monocytes and induce their differentiation into M2-like macrophages. Together these cytokines perpetuate the CSC-promoting interactions between CSCs and TAMs. Indeed, admixed TAMs promote the tumor-initiating ability of CSCs whereas ablation of endogenous macrophages substantially diminished tumor initiation. Importantly, the juxtaposition of TAMs with the mesenchymal-like CD90high CSCs can be observed at the invading edge in primary human breast tumor sections and xenograft tumors. On the contrary, we rarely find TAMS infiltrating beyond the edge of tumors into the regions where the CD90neg non-stem carcinoma cells reside. These findings underscore the importance of TAMs as critical components of the CSC niche and highlight their potential as therapeutics targets. Citation Format: Haihui Lu, Wai Leong Tam, Vera Donnenberg, Xin Ye, Rohit Bhargava, Robert Weinberg. Juxtacrine signaling between the tumor-associated macrophages and the breast cancer stem cells contribute to the cancer stem cell niche by inducing a cytokine signaling network. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B150.
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a breast cancer stem cell niche supported by Juxtacrine Signalling from monocytes and macrophages
Nature Cell Biology, 2014Co-Authors: Haihui Lu, Karl R Clauser, Julia Frose, Xin Ye, Elinor Ng Eaton, Ferenc Reinhardt, Vera S Donnenberg, Rohit BhargavaAbstract:Weinberg and colleagues report that monocytes and macrophages interact with stem-like human mammary epithelial cells to create a breast cancer stem cell niche.
