The Experts below are selected from a list of 34137 Experts worldwide ranked by ideXlab platform
Milena Villarroel - One of the best experts on this subject based on the ideXlab platform.
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the cancer related transcription factor runx2 modulates expression and secretion of the matricellular protein osteopontin in Osteosarcoma cells to promote adhesion to endothelial pulmonary cells and lung metastasis
Journal of Cellular Physiology, 2019Co-Authors: Francisco Villanueva, Hector Araya, Pedro Briceno, Nelson Varela, Andres Stevenson, Sofia Jerez, Fabian Tempio, Jonas Chnaiderman, Carola Perez, Milena VillarroelAbstract:Osteosarcomas are bone tumors that frequently metastasize to the lung. Aberrant expression of the transcription factor, runt-related transcription factor 2 (RUNX2), is a key pathological feature in Osteosarcoma and associated with loss of p53 and miR-34 expression. Elevated RUNX2 may transcriptionally activate genes mediating tumor progression and metastasis, including the RUNX2 target gene osteopontin (OPN/SPP1). This gene encodes a secreted matricellular protein produced by osteoblasts to regulate bone matrix remodeling and tissue calcification. Here we investigated whether and how the RUNX2/OPN axis regulates lung metastasis of Osteosarcoma. Importantly, RUNX2 depletion attenuates lung metastasis of Osteosarcoma cells in vivo. Using next-generation RNA-sequencing, protein-based assays, as well as the loss- and gain-of-function approaches in selected Osteosarcoma cell lines, we show that osteopontin messenger RNA levels closely correlate with RUNX2 expression and that RUNX2 controls the levels of secreted osteopontin. Elevated osteopontin levels promote heterotypic cell-cell adhesion of Osteosarcoma cells to human pulmonary microvascular endothelial cells, but not in the presence of neutralizing antibodies. Collectively, these findings indicate that the RUNX2/OPN axis regulates the ability of Osteosarcoma cells to attach to pulmonary endothelial cells as a key step in metastasis of Osteosarcoma cells to the lung.
Huizhong Zhang - One of the best experts on this subject based on the ideXlab platform.
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inhibiting proliferation and enhancing chemosensitivity to taxanes in Osteosarcoma cells by rna interference mediated downregulation of stathmin expression
Molecular Medicine, 2007Co-Authors: Rui Wang, Shiyin Cheng, Ke Dong, Xi Wang, Huizhong ZhangAbstract:Stathmin (Oncoprotein18), a signal transduction regulatory factor, plays an Important role In cell division and malignant tumor development. Stathmin is a ubiquitous intracellular phosphoprotein that is overexpressed in a variety of human malignancies, including Osteosarcoma. To investigate the potential use of stathmin as a therapeutic target for human Osteosarcomas, we employed RNA interference [small interfering RNA (siRNA)] to reduce stathmin expression in human Osteosarcoma cell lines and analyzed their phenotypic changes. Results showed that the downregulation of stathmin expression in human Osteosarcoma cells significantly inhibited cell proliferation in vitro and tumorigenicity in vivo. The specific downregulation induced cell arrest in the G2/M phase of cell cycle and eventually apoptotic cell death. Taxanes are a group of effective chemotherapeutic agents whose activity is mediated through stabilization of the microtubules of the mitotic spindle. In the present study, we also observed a synergistic enhancement of the cytotoxicity effect by combination use of taxanes and RNA interference-mediated stathmin downregulation. All these experimental data indicate that stathmin downregulation can lead to potent antitumor activity and chemosensitizing activity to taxanes in human Osteosarcomas.
Francisco Villanueva - One of the best experts on this subject based on the ideXlab platform.
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the cancer related transcription factor runx2 modulates expression and secretion of the matricellular protein osteopontin in Osteosarcoma cells to promote adhesion to endothelial pulmonary cells and lung metastasis
Journal of Cellular Physiology, 2019Co-Authors: Francisco Villanueva, Hector Araya, Pedro Briceno, Nelson Varela, Andres Stevenson, Sofia Jerez, Fabian Tempio, Jonas Chnaiderman, Carola Perez, Milena VillarroelAbstract:Osteosarcomas are bone tumors that frequently metastasize to the lung. Aberrant expression of the transcription factor, runt-related transcription factor 2 (RUNX2), is a key pathological feature in Osteosarcoma and associated with loss of p53 and miR-34 expression. Elevated RUNX2 may transcriptionally activate genes mediating tumor progression and metastasis, including the RUNX2 target gene osteopontin (OPN/SPP1). This gene encodes a secreted matricellular protein produced by osteoblasts to regulate bone matrix remodeling and tissue calcification. Here we investigated whether and how the RUNX2/OPN axis regulates lung metastasis of Osteosarcoma. Importantly, RUNX2 depletion attenuates lung metastasis of Osteosarcoma cells in vivo. Using next-generation RNA-sequencing, protein-based assays, as well as the loss- and gain-of-function approaches in selected Osteosarcoma cell lines, we show that osteopontin messenger RNA levels closely correlate with RUNX2 expression and that RUNX2 controls the levels of secreted osteopontin. Elevated osteopontin levels promote heterotypic cell-cell adhesion of Osteosarcoma cells to human pulmonary microvascular endothelial cells, but not in the presence of neutralizing antibodies. Collectively, these findings indicate that the RUNX2/OPN axis regulates the ability of Osteosarcoma cells to attach to pulmonary endothelial cells as a key step in metastasis of Osteosarcoma cells to the lung.
Upal Basuroy - One of the best experts on this subject based on the ideXlab platform.
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Osteosarcoma cell proliferation and survival requires mglur5 receptor activity and is blocked by riluzole
PLOS ONE, 2017Co-Authors: Sally Liao, Yuleisy Ruiz, Hira Gulzar, Zarina Yelskaya, Lyes Ait Taouit, Murielle Houssou, Trisha Jaikaran, Yuriy Schvarts, Kristina Kozlitina, Upal BasuroyAbstract:Osteosarcomas are malignant tumors of bone, most commonly seen in children and adolescents. Despite advances in modern medicine, the poor survival rate of metastatic Osteosarcoma has not improved in two decades. In the present study we have investigated the effect of Riluzole on a human and mouse metastatic Osteosarcoma cells. We show that LM7 cells secrete glutamate in the media and that mGluR5 receptors are required for the proliferation of LM7 cells. Riluzole, which is known to inhibit glutamate release, inhibits proliferation, induces apoptosis and prevents migration of LM7 cells. This is also seen with Fenobam, a specific blocker of mGluR5. We also show that Riluzole alters the phosphorylation status of AKT/P70 S6 kinase, ERK1/2 and JNK1/2. Thus Riluzole is an effective drug to inhibit proliferation and survival of Osteosarcoma cells and has therapeutic potential for the treatment of Osteosarcoma exhibiting autocrine glutamate signaling.
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sox2 maintains self renewal of tumor initiating cells in Osteosarcomas
Oncogene, 2012Co-Authors: Upal Basuroy, Alka Mansukhani, Eunjeong Seo, Lalitha Ramanathapuram, Timothy B Rapp, Jennifer A Perry, Stuart H Orkin, Claudio BasilicoAbstract:Tumors are thought to be sustained by a reservoir of self-renewing cells, termed tumor initiating cells or cancer stem cells. Osteosarcomas are high-grade sarcomas derived from osteoblast progenitor cells and are the most common pediatric bone malignancy. In this report we show that the stem cell transcription factor Sox2 is highly expressed in human and murine Osteosarcoma cell lines as well as in tumor samples. Osteosarcoma cells have increased ability to grow in suspension as osteospheres, that are greatly enriched in expression of Sox2 and the stem cell marker, Sca-1. Depletion of Sox2 by shRNAs in independent murine Osteosarcoma-derived cells drastically reduces their transformed properties in vitro and their ability to form tumors. Sox2-depleted Osteosarcoma cells can no longer form osteospheres, and differentiate into mature osteoblasts. Concomitantly, they exhibit decreased Sca-1 expression and upregulation of the Wnt signaling pathway. Thus, despite other mutations, these tumor cells maintain a proliferative requirement for Sox2. Our data indicate that Sox2 is required for Osteosarcoma cell self-renewal, and that Sox2 antagonizes the pro-differentiation Wnt pathway, that can in turn reduce Sox2 expression. These studies define Sox2 as a survival factor and a novel biomarker of self-renewal in Osteosarcomas, and support a tumor suppressive role for the Wnt pathway in tumors of mesenchymal origin. Our findings could provide the basis for novel therapeutic strategies based on inhibiting Sox2 or enhancing Wnt signaling for the treatment of Osteosarcomas.
Rui Wang - One of the best experts on this subject based on the ideXlab platform.
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inhibiting proliferation and enhancing chemosensitivity to taxanes in Osteosarcoma cells by rna interference mediated downregulation of stathmin expression
Molecular Medicine, 2007Co-Authors: Rui Wang, Shiyin Cheng, Ke Dong, Xi Wang, Huizhong ZhangAbstract:Stathmin (Oncoprotein18), a signal transduction regulatory factor, plays an Important role In cell division and malignant tumor development. Stathmin is a ubiquitous intracellular phosphoprotein that is overexpressed in a variety of human malignancies, including Osteosarcoma. To investigate the potential use of stathmin as a therapeutic target for human Osteosarcomas, we employed RNA interference [small interfering RNA (siRNA)] to reduce stathmin expression in human Osteosarcoma cell lines and analyzed their phenotypic changes. Results showed that the downregulation of stathmin expression in human Osteosarcoma cells significantly inhibited cell proliferation in vitro and tumorigenicity in vivo. The specific downregulation induced cell arrest in the G2/M phase of cell cycle and eventually apoptotic cell death. Taxanes are a group of effective chemotherapeutic agents whose activity is mediated through stabilization of the microtubules of the mitotic spindle. In the present study, we also observed a synergistic enhancement of the cytotoxicity effect by combination use of taxanes and RNA interference-mediated stathmin downregulation. All these experimental data indicate that stathmin downregulation can lead to potent antitumor activity and chemosensitizing activity to taxanes in human Osteosarcomas.
