Ido Nevo - Academia.edu (original) (raw)

Papers by Ido Nevo

Research paper thumbnail of Identification of Molecular Pathways Facilitating Glioma Cell Invasion In Situ

Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific thera... more Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion. In this study, we used a unique microarray profiling approach on a human glioma stem cell (GSC) xenograft model to explore gene expression changes in situ in Invading Glioma Cells (IGCs) compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex. IGCs were found to have reduced expression of genes within the extracellular matrix compartment, and genes involved in cell adhesion, cell polarity and epithelial to mesenchymal transition (EMT) processes. The infiltrated microenvironment showed activation of wound repair and tissue remodeling networks. We confirmed by protein analysis t...

Research paper thumbnail of www.neoplasia.com Generation and Characterization of Novel Local and Metastatic

Neuroblastoma (NB) is the most commonly occurring solid tumor in children. The disease usually ar... more Neuroblastoma (NB) is the most commonly occurring solid tumor in children. The disease usually arises in the adrenal medulla, and it is characterized by a remarkable heterogeneity in its progression. Most NB patients with an advanced disease have massive bone marrow infiltration at diagnosis. Lung metastasis represents a widely disseminated stage and is typically considered to be a terminal event. Much like other malignancies, NB progression is a complex, multistep process. The expression, function, and significance of the various factors involved in NB progression must be studied in relevant in vivo and in vitro models. Currently, models consisting of metastatic and nonmetastatic cell variants of the same genetic background exist for several types of cancer; however, none exists for NB. In the present study, we describe the generation of a NB metastasis model. SH-SY5Y and MHH-NB-11 NB cells were inoculated orthotopically into the adrenal glands of athymic nude mice. Neuroblastoma c...

Research paper thumbnail of Hexokinase 2 is a determinant of neuroblastoma metastasis

British Journal of Cancer, 2016

Research paper thumbnail of Generation and characterization of novel local and metastatic human neuroblastoma variants

Neoplasia (New York, N.Y.), 2008

Neuroblastoma (NB) is the most commonly occurring solid tumor in children. The disease usually ar... more Neuroblastoma (NB) is the most commonly occurring solid tumor in children. The disease usually arises in the adrenal medulla, and it is characterized by a remarkable heterogeneity in its progression. Most NB patients with an advanced disease have massive bone marrow infiltration at diagnosis. Lung metastasis represents a widely disseminated stage and is typically considered to be a terminal event. Much like other malignancies, NB progression is a complex, multistep process. The expression, function, and significance of the various factors involved in NB progression must be studied in relevant in vivo and in vitro models. Currently, models consisting of metastatic and nonmetastatic cell variants of the same genetic background exist for several types of cancer; however, none exists for NB. In the present study, we describe the generation of a NB metastasis model. SH-SY5Y and MHH-NB-11 NB cells were inoculated orthotopically into the adrenal glands of athymic nude mice. Neuroblastoma c...

Research paper thumbnail of Gene-expression-based analysis of local and metastatic neuroblastoma variants reveals a set of genes associated with tumor progression in neuroblastoma patients

International Journal of Cancer, 2000

Gene-expression-based analysis of local and metastatic neuroblastoma variants reveals a set of ge... more Gene-expression-based analysis of local and metastatic neuroblastoma variants reveals a set of genes associated with.

Research paper thumbnail of The tumor microenvironment: CXCR4 is associated with distinct protein expression patterns in neuroblastoma cells

Immunology Letters, 2004

In previous studies, we demonstrated that human neuroblastoma cells are equipped with the machine... more In previous studies, we demonstrated that human neuroblastoma cells are equipped with the machinery to direct their homing to bone marrow. These tumor cells express the CXCR4 receptor for the bone marrow stroma-derived chemokine CXCL12 (SDF-1) and secrete the CXCL12 ligand. The present study was undertaken to explore possible differences in gene-expression patterns between neuroblastoma variants that over-express CXCR4 (designated STH cells) and those which express very little of this receptor (STL cells). The results of the study clearly indicate that these variants show a differential gene-expression profile. They differ in expression of some integrins such as VLA2, VLA3 and VLA6, of neuroendocrine-markers such as CD56 and synaptophysin, in the expression of c-kit and in the secretion of certain cytokines and growth factors such as TNF␣, SDF-1, VEGF, IL-8, GM-CSF and IP-10. We hypothesize that these differences are due to an autocrine SDF-1␣-CXCR4 axis.

Research paper thumbnail of Cellular characteristics of neuroblastoma cells: regulation by the ELR−-CXC chemokine CXCL10 and expression of a CXCR3-like receptor

Cytokine, 2005

Bone marrow stroma cells secrete the chemokine CXCL12 that may support bone marrow metastasis for... more Bone marrow stroma cells secrete the chemokine CXCL12 that may support bone marrow metastasis formation by neuroblastoma cells. The present study demonstrates that bone marrow stroma cell lines also secrete CXCL10, a chemokine that was shown in the past to have anti-malignancy functions. A receptor recognized by antibodies against CXCR3 was shown to be expressed by six neuroblastoma cell lines. Further detailed analysis was performed on the NUB6 and SK-NMC neuroblastoma cells, showing that CXCL10 induced potent Erk phosphorylation in a G(alpha)i-dependent manner. The role of a CXCR3-like receptor in Erk phosphorylation was substantiated by the ability of CXCL11, another potent CXCR3 ligand, to induce Erk phosphorylation in the NUB6 and SK-NMC cells. Further characterization of CXCL10 activities indicated that CXCL10 partly inhibited the growth of the NUB6 and SK-NMC cells. Both NUB6 and SK-NMC cells did not migrate to CXCL10, although their migratory machinery was intact, as evidenced by their migration to bone marrow constituents. Altogether, these results suggest that CXCL10 interacts with a CXCR3-like receptor in neuroblastoma cell lines, raising the possibility that following the homing of the tumor cells to the bone marrow (through a CXCL10-independent mechanism), CXCL10 may partly inhibit neuroblastoma cell growth at this site.

Research paper thumbnail of The involvement of the fractalkine receptor in the transmigration of neuroblastoma cells through bone-marrow endothelial cells

Cancer Letters, 2009

Transendothelial migration (TEM) of tumor cells is a crucial step in metastasis formation. The pr... more Transendothelial migration (TEM) of tumor cells is a crucial step in metastasis formation. The prevailing paradigm is that the mechanism underlying TEM of tumor cells is similar to that of leukocytes involving adhesion molecules and chemokines.

Research paper thumbnail of Lung-Residing Metastatic and Dormant Neuroblastoma Cells

The American Journal of Pathology, 2011

The primer designation indicates the first nucleotide according to sequences derived from the Nat... more The primer designation indicates the first nucleotide according to sequences derived from the National Center for Biotechnology Information database and the direction of the primer, sense (S) or anti-sense (AS).

Research paper thumbnail of Identification of molecular pathways facilitating glioma cell invasion in situ

PloS one, 2014

Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific thera... more Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion. In this study, we used a unique microarray profiling approach on a human glioma stem cell (GSC) xenograft model to explore gene expression changes in situ in Invading Glioma Cells (IGCs) compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex. IGCs were found to have reduced expression of genes within the extracellular matrix compartment, and genes involved in cell adhesion, cell polarity and epithelial to mesenchymal transition (EMT) processes. The infiltrated microenvironment showed activation of wound repair and tissue remodeling networks. We confirmed by protein analysis t...

Research paper thumbnail of Identification of Molecular Pathways Facilitating Glioma Cell Invasion In Situ

Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific thera... more Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion. In this study, we used a unique microarray profiling approach on a human glioma stem cell (GSC) xenograft model to explore gene expression changes in situ in Invading Glioma Cells (IGCs) compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex. IGCs were found to have reduced expression of genes within the extracellular matrix compartment, and genes involved in cell adhesion, cell polarity and epithelial to mesenchymal transition (EMT) processes. The infiltrated microenvironment showed activation of wound repair and tissue remodeling networks. We confirmed by protein analysis t...

Research paper thumbnail of www.neoplasia.com Generation and Characterization of Novel Local and Metastatic

Neuroblastoma (NB) is the most commonly occurring solid tumor in children. The disease usually ar... more Neuroblastoma (NB) is the most commonly occurring solid tumor in children. The disease usually arises in the adrenal medulla, and it is characterized by a remarkable heterogeneity in its progression. Most NB patients with an advanced disease have massive bone marrow infiltration at diagnosis. Lung metastasis represents a widely disseminated stage and is typically considered to be a terminal event. Much like other malignancies, NB progression is a complex, multistep process. The expression, function, and significance of the various factors involved in NB progression must be studied in relevant in vivo and in vitro models. Currently, models consisting of metastatic and nonmetastatic cell variants of the same genetic background exist for several types of cancer; however, none exists for NB. In the present study, we describe the generation of a NB metastasis model. SH-SY5Y and MHH-NB-11 NB cells were inoculated orthotopically into the adrenal glands of athymic nude mice. Neuroblastoma c...

Research paper thumbnail of Hexokinase 2 is a determinant of neuroblastoma metastasis

British Journal of Cancer, 2016

Research paper thumbnail of Generation and characterization of novel local and metastatic human neuroblastoma variants

Neoplasia (New York, N.Y.), 2008

Neuroblastoma (NB) is the most commonly occurring solid tumor in children. The disease usually ar... more Neuroblastoma (NB) is the most commonly occurring solid tumor in children. The disease usually arises in the adrenal medulla, and it is characterized by a remarkable heterogeneity in its progression. Most NB patients with an advanced disease have massive bone marrow infiltration at diagnosis. Lung metastasis represents a widely disseminated stage and is typically considered to be a terminal event. Much like other malignancies, NB progression is a complex, multistep process. The expression, function, and significance of the various factors involved in NB progression must be studied in relevant in vivo and in vitro models. Currently, models consisting of metastatic and nonmetastatic cell variants of the same genetic background exist for several types of cancer; however, none exists for NB. In the present study, we describe the generation of a NB metastasis model. SH-SY5Y and MHH-NB-11 NB cells were inoculated orthotopically into the adrenal glands of athymic nude mice. Neuroblastoma c...

Research paper thumbnail of Gene-expression-based analysis of local and metastatic neuroblastoma variants reveals a set of genes associated with tumor progression in neuroblastoma patients

International Journal of Cancer, 2000

Gene-expression-based analysis of local and metastatic neuroblastoma variants reveals a set of ge... more Gene-expression-based analysis of local and metastatic neuroblastoma variants reveals a set of genes associated with.

Research paper thumbnail of The tumor microenvironment: CXCR4 is associated with distinct protein expression patterns in neuroblastoma cells

Immunology Letters, 2004

In previous studies, we demonstrated that human neuroblastoma cells are equipped with the machine... more In previous studies, we demonstrated that human neuroblastoma cells are equipped with the machinery to direct their homing to bone marrow. These tumor cells express the CXCR4 receptor for the bone marrow stroma-derived chemokine CXCL12 (SDF-1) and secrete the CXCL12 ligand. The present study was undertaken to explore possible differences in gene-expression patterns between neuroblastoma variants that over-express CXCR4 (designated STH cells) and those which express very little of this receptor (STL cells). The results of the study clearly indicate that these variants show a differential gene-expression profile. They differ in expression of some integrins such as VLA2, VLA3 and VLA6, of neuroendocrine-markers such as CD56 and synaptophysin, in the expression of c-kit and in the secretion of certain cytokines and growth factors such as TNF␣, SDF-1, VEGF, IL-8, GM-CSF and IP-10. We hypothesize that these differences are due to an autocrine SDF-1␣-CXCR4 axis.

Research paper thumbnail of Cellular characteristics of neuroblastoma cells: regulation by the ELR−-CXC chemokine CXCL10 and expression of a CXCR3-like receptor

Cytokine, 2005

Bone marrow stroma cells secrete the chemokine CXCL12 that may support bone marrow metastasis for... more Bone marrow stroma cells secrete the chemokine CXCL12 that may support bone marrow metastasis formation by neuroblastoma cells. The present study demonstrates that bone marrow stroma cell lines also secrete CXCL10, a chemokine that was shown in the past to have anti-malignancy functions. A receptor recognized by antibodies against CXCR3 was shown to be expressed by six neuroblastoma cell lines. Further detailed analysis was performed on the NUB6 and SK-NMC neuroblastoma cells, showing that CXCL10 induced potent Erk phosphorylation in a G(alpha)i-dependent manner. The role of a CXCR3-like receptor in Erk phosphorylation was substantiated by the ability of CXCL11, another potent CXCR3 ligand, to induce Erk phosphorylation in the NUB6 and SK-NMC cells. Further characterization of CXCL10 activities indicated that CXCL10 partly inhibited the growth of the NUB6 and SK-NMC cells. Both NUB6 and SK-NMC cells did not migrate to CXCL10, although their migratory machinery was intact, as evidenced by their migration to bone marrow constituents. Altogether, these results suggest that CXCL10 interacts with a CXCR3-like receptor in neuroblastoma cell lines, raising the possibility that following the homing of the tumor cells to the bone marrow (through a CXCL10-independent mechanism), CXCL10 may partly inhibit neuroblastoma cell growth at this site.

Research paper thumbnail of The involvement of the fractalkine receptor in the transmigration of neuroblastoma cells through bone-marrow endothelial cells

Cancer Letters, 2009

Transendothelial migration (TEM) of tumor cells is a crucial step in metastasis formation. The pr... more Transendothelial migration (TEM) of tumor cells is a crucial step in metastasis formation. The prevailing paradigm is that the mechanism underlying TEM of tumor cells is similar to that of leukocytes involving adhesion molecules and chemokines.

Research paper thumbnail of Lung-Residing Metastatic and Dormant Neuroblastoma Cells

The American Journal of Pathology, 2011

The primer designation indicates the first nucleotide according to sequences derived from the Nat... more The primer designation indicates the first nucleotide according to sequences derived from the National Center for Biotechnology Information database and the direction of the primer, sense (S) or anti-sense (AS).

Research paper thumbnail of Identification of molecular pathways facilitating glioma cell invasion in situ

PloS one, 2014

Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific thera... more Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion. In this study, we used a unique microarray profiling approach on a human glioma stem cell (GSC) xenograft model to explore gene expression changes in situ in Invading Glioma Cells (IGCs) compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex. IGCs were found to have reduced expression of genes within the extracellular matrix compartment, and genes involved in cell adhesion, cell polarity and epithelial to mesenchymal transition (EMT) processes. The infiltrated microenvironment showed activation of wound repair and tissue remodeling networks. We confirmed by protein analysis t...