Human neuroblastoma cells produce extracellular matrix-degrading enzymes, induce endothelial cell proliferation and are angiogenicin vivo

Ribatti, Doménico; Alessandri, Giulio; Vacca, Angelo; Iurlaro, Monica; Ponzoni, Mirco

doi:10.1002/(sici)1097-0215(19980729)77:3<449::aid-ijc22>3.0.co;2-1

Cited by 53 publications

(12 citation statements)

References 15 publications

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“…SHEP/N-Myc/Bcl-2 cells, which are tumorigenic in both in vitro and in vivo assays (Jasty et al, 2001), show a large increase in MMP-2 expression, secretion, and activation. Our data agree with MMP-2 pro®les in other neuroblastoma cell lines (Taguchi et al, 1997;Ribatti et al, 1998;Bjornland et al, 2001). Previous works show that there is no increase in MMP-2 activity in cell lines displaying only ampli®ed N-Myc (Taguchi et al, 1997).…”

Section: Discussionsupporting

confidence: 91%

“…Current hypotheses suggest that MMP activation promotes tumor invasion through degradation of basement membrane components and metastases through increased cellular intravasation through endothelial cells into the blood stream (Stamenkovic, 2000). Many tumor types have increased MMP activation corresponding to an increased malignant phenotype, including neuroblastoma (Ara et al, 1998(Ara et al, , 2000Ribatti et al, 1998;Sugiura et al, 1998). Neuroblastoma is a pediatric tumor composed of several cell types, including neuroblasts, chrondrocytes, glial cells, and melanocytes, which have varying degrees of tumorigenic potential (Shimada et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…The current study investigates the expression and secretion of MMP-2, the gelatinase most correlated with advanced stage neuroblastoma tumors (Ribatti et al, 1998;de Veas et al, 1995;Ara et al, 2000). SHEP/Vector, SHEP/N-Myc, SHEP/Bcl-2, and SHEP/N-Myc/Bcl-2 cells were plated on either plastic tissue culture dishes or Matrigel arti®cial basement membrane-coated dishes to stimulate MMP activation.…”

Section: Mmp-2 Is Regulated By N-myc and Bcl-2mentioning

confidence: 99%

“…During tumor development, MMP activation promotes tumor invasion and metastasis through degradation of basement membrane and either invasion into surrounding tissue or intravasation through endothelial cells into the blood stream (Stamenkovic, 2000). Several cancers show increased MMP activation, including breast carcinoma (Du y et al, 2000), bladder carcinoma (Kanayama, 2001), multiple myeloma (Kelly et al, 2000), and neuroblastoma (Ara et al, 1998(Ara et al, , 2000Ribatti et al, 1998;Sugiura et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells

Noujaim

Golen

et al. 2002

Oncogene

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Mmp-2 Is Regulated By N-myc and Bcl-2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells

Noujaim

Golen

et al. 2002

Oncogene

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“…TSP-1 also inhibits the activity of matrix metalloproteinase-9 (MMP-9) (Ribatti et al, 1998;Rodriguez-Manzaneque et al, 2001). TSP-1 inhibits angiogenesis by binding to the CD36 receptor protein, which is present on the endothelial cell surface (Dawson et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

et al. 2006

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We determined the impact of HER2 signaling on two proangiogenic factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), and on an antiangiogenic factor, thrombospondin-1 (TSP-1). Re-expression of HER2 in MCF-7 and T-47D breast cancer cells that endogenously express low levels of HER2 resulted in elevated expression of VEGF and IL-8 and decreased expression of TSP-1. Inhibition of HER2 with a humanized anti-HER2 antibody (trastuzumab, or Herceptin s ) or a retrovirus-mediated small interfering RNA against HER2 (siHER2) decreased VEGF and IL-8 expression, but increased TSP-1 expression in BT474 breast cancer cells that express high levels of HER2. These in vitro results were further evaluated by treatment of BT474 xenografts in immunosuppressed mice with trastuzumab. Trastuzumab inhibited growth of BT474 xenografts and decreased microvascular density associated with downregulation of VEGF and IL-8 and with upregulation of TSP-1 expression. Inhibiting the PI3K-AKT pathway decreased VEGF and IL-8 expression. AKT1 overexpession increased VEGF and IL-8 expression, but did not increase TSP-1 expression. A p38 kinase inhibitor, SB203580, instead blocked TSP-1 expression and a p38 activator, MKK6, increased TSP-1 expression. Trastuzumab stimulated sustained p38 activation and SB203580 attenuated the TSP-1 upregulation induced by trastuzumab. HER2 signaling therefore influences the equilibrium between pro-and antiangiogenic factors via distinct signaling pathways. Trastuzumab inhibits angiogenesis and tumor growth, at least in part, through activation of the HER2-p38-TSP-1 pathway and inhibition of the HER2-PI3K-AKT-VEGF/IL-8 pathway.

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Flavopiridol inhibits vascular endothelial growth factor production induced by hypoxia or picolinic acid in human neuroblastoma

Rapella

Negrioli

Melillo

et al. 2002

Intl Journal of Cancer

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Human neuroblastoma (NB) tumors elaborate angiogenic peptides, and enhanced angiogenesis correlates with their aggressive behavior, metastatic spread and poor clinical outcome. Hence, inhibition of angiogenic factor production may represent a potential therapeutic target for NB treatment. There is currently little information regarding the stimuli that control NB production of angiogenic mediators. In this study, we analyzed the effects of hypoxia, a common feature of solid tumors and a major drive to tumor angiogenesis, and of PA, a tryptophan catabolite produced under inflammatory conditions and endowed with several biologic properties, on the production of the angiogenic activator VEGF by advanced-stage human NB cell lines. We demonstrate that both stimuli are potent inducers of VEGF expression and secretion. VEGF upregulation by PA involved iron chelation because iron sulfate prevented this effect whereas the ironchelating agent DFX induced VEGF production. Conversely, the CDK inhibitor Flp completely blocked VEGF induction by hypoxia. This effect occurred as early as 3 hr after stimulation and did not require de novo protein synthesis. Moreover, Flp exerted similar inhibitory activity on VEGF induction by PA or DFX, suggesting that this compound targets an essential step in the signaling pathway that leads to VEGF expression. Our findings demonstrate that PA can modulate angiogenic factor production by tumor cells and establish the importance of Flp as an inhibitor of VEGF production by human NB. © 2002 Wiley-Liss, Inc. Key words: neuroblastoma; flavopiridol; picolinic acid; vascular endothelial growth factor; hypoxiaNeuroblastoma (NB) is the most common pediatric solid tumor that arises from the sympathetic nervous system. 1 Low-stage, localized NB tumors often spontaneously regress or mature to benign forms, whereas high-stage, disseminated tumors are rapidly progressive and associated with poor outcome. 2 NB tumors are characterized by genetic changes that correlate with patients' prognosis, e.g., MYCN amplification, 1p LOH deletion and 17q trisomy. 3,4 Despite aggressive therapeutic protocols, children who develop advanced-stage NB over the age of 1 year often have a poor prognosis associated with local growth and metastatic spread. 2,5 Malignant solid tumors depend on neoangiogenesis for their progressive growth and metastatization. 6 Proliferating tumor cells acquire the ability of triggering an angiogenic response through the production of diffusible angiogenic factors that promote tumor growth and spreading. 7 Human NB elaborate angiogenic peptides, 8 stimulate endothelial cell proliferation in vitro and in vivo 9 and induce angiogenesis in nude mice during tumorigenesis. 10 Moreover, Meitar et al. 11 found that NB angiogenesis correlates with metastatic disease, MYCN amplification and poor clinical outcome, suggesting the importance of angiogenesis in NB progression. Hence, pharmacologic intervention to target angiogenic factor production by NB is an attractive possibility with potential therapeut...

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Human neuroblastoma cells produce extracellular matrix-degrading enzymes, induce endothelial cell proliferation and are angiogenicin vivo

Cited by 53 publications

References 15 publications

N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells

N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells

HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

Flavopiridol inhibits vascular endothelial growth factor production induced by hypoxia or picolinic acid in human neuroblastoma

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