Receptors and effects of the inhibitory neuropeptide somatostatin in microglial cells

Feindt, Janka; Schmidt, Andreas; Mentlein, Rolf

doi:10.1016/s0169-328x(98)00184-3

Cited by 40 publications

(23 citation statements)

References 25 publications

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“…The activation of these receptors by somatostatin per se or by metabolically stable analog octreotide (SMS 201-995, selective agonist of sst2, sst3, and sst5 receptors) induced protein phosphorylation and inhibited microglial proliferation (272).…”

Section: G Somatostatin Receptorsmentioning

confidence: 99%

Physiology of Microglia

Kettenmann

Hanisch

Нода

et al. 2011

Physiological Reviews

3,144

2,981

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Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed “resting microglia.” Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the “activated microglial cell.” This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

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Section: G Somatostatin Receptorsmentioning

confidence: 99%

Physiology of Microglia

Kettenmann

Hanisch

Нода

et al. 2011

Physiological Reviews

3,144

2,981

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“…Purity of the culture was controlled routinely by immunostaining for the cell type specific markers glial fibrillary acidic protein (GFAP, astrocytes/glioblastoma cells; antibody from Boehringer, Mannheim Germany) and CD68 (contaminating microglial cells and macrophages). 21 Contaminations by Mycoplasma were checked by staining with bisbenzimide (Merck, Darmstadt, Germany).…”

Section: Cell Culture and Tissue Samplesmentioning

confidence: 99%

Matrix‐degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas

Held‐Feindt

Paredes

Blömer

et al. 2005

Intl Journal of Cancer

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128

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Brain tumors, in particular glioblastomas, have a high morbidity and mortality, mainly due to their invasive nature. A prerequisite for this invasiveness is cell migration based on increased expression of proteases digesting the extracellular matrix. Brevican, an important extracellular proteoglycan that is upregulated in glioblastomas, can be degraded by certain proteases. We demonstrate that in human glioblastomas secretory proteases like ADAMTS4 and ADAMTS5 (aggrecanases 1 and 2; ADAMTS 5 a disintegrin and metalloproteinase with thrombospondin motifs) are expressed on the mRNA and protein levels in considerable amounts. Realtime RT-PCR shows a higher levels of ADAMTS4 and 5 expressions in glioblastomas in situ, compared to cultured human glioblastoma cells. The upregulation of these proteases in vivo by cytokines may explain this difference. In vitro, transforming growth factor-b induces ADAMTS4, but less ADAMTS5, and interleukin1b ADAMTS5, but not ADAMTS4. As demonstrated by immunohistochemistry and confocal microscopy in situ, ADAMTS5 expression is confined to proliferating glioblastoma cells of surgical tumor sections and with lower intensity to astroglial cells in normal brain sections, as opposed to brevican. In vitro, glioblastoma-derived ADAMTS5 degrades recombinant human brevican to several smaller fragments. Our results show that ADAMTS4 and 5 are upregulated on proliferating glioblastoma cells and these proteases may contribute to their invasive potential. ' 2005 Wiley-Liss, Inc.Key words: glioblastoma; invasion; proteases; extracellular matrix; degradation; cytokines High-grade glial tumors (anaplastic astrocytoma and glioblastoma multiforme) are the most frequent brain tumors in adults. 1,2 Despite multimodal therapeutic efforts, the mean survival time is only 9-12 months for glioblastoma multiforme (WHO Grade IV) and 2 years for anaplastic astrocytoma (WHO Grade III). The ability of individual tumor cells to infiltrate brain tissue is the primary reason for this poor prognosis. Individual tumor cells (''guerrilla cells'') can migrate more than 4.0-7.0 cm from the gross tumor into the surrounding normal brain tissue. 3 In part, the migratory and invasive behavior is a consequence of tumor cell interaction with specific components of the extracellular matrix (ECM). Brain ECM components include laminin, collagen IV, tenascin, fibronectin and proteoglycans. 4 The glycosaminoglycan hyaluronic acid (HA) plays a central role in cellular proliferation, differentiation and migration, and may be a key element in tumor spreading. 5 BEHAB (brain enriched hyaluronan binding)/brevican is a recently identified HA binding protein that belongs to the lectican family. 6-9 BEHAB/brevican expression is developmentally regulated in the central nervous system, in particular during periods of glial cell proliferation and migration. 9 Accordingly, BEHAB/brevican is upregulated in the vast majority of surgical glioblastomas, 9-11 and expression levels and proteolytic cleavage of BEHAB/brevican seem to correlate with tumo...

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“…All cultures were Ͼ95% immunopositive for the astroglial/glioma marker glial fibrillar acidic protein (GFAP; antibody from Boehringer-Mannheim, Mannheim, Germany) and nonor Ͻ1% (cultivated solid gliomas) reactive with the macrophage/ microglial marker CD68. 18 Experiments were performed with cells after passages 3 to 6 (gliomas) or 5 to 15 (cell lines).…”

Section: Cell Culturesmentioning

confidence: 99%

Somatostatin inhibits the production of vascular endothelial growth factor in human glioma cells

et al. 2001

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In various cell types, the neuro-and endocrine peptide somatostatin induces inhibitory and anti-secretory effects. Since somatostatin receptors, especially of the subtype sst2A, are constantly over-expressed in gliomas, we investigated the influence of somatostatin and the receptor subtype-selective peptide/non-peptide agonists octreotide and L-054,522 on the secretion of the most important angiogenesis factor produced by gliomas, vascular endothelial growth factor (VEGF). Cultivated cells from solid human gliomas of different stages and glioma cell lines secreted variable amounts of VEGF, which could be lowered to 25% to 80% by co-incubation with somatostatin or sst2-selective agonists (octreotide and L-054,522). These effects were dose-dependent at nanomolar concentrations. Stimulation with different growth factors (EGF, bFGF) or hypoxia considerably increased VEGF production over basal levels. Growth factorinduced VEGF synthesis could be suppressed to <50% by co-incubation with somatostatin or an sst2-selective agonist; this was less pronounced in hypoxia-induced VEGF synthesis. The effects were detected at the protein and mRNA levels. These experiments indicate a potent anti-secretory action of somatostatin or sst2 agonists on human glioma cells that may be useful for inhibiting angiogenesis in these tumors.

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Receptors and effects of the inhibitory neuropeptide somatostatin in microglial cells

Cited by 40 publications

References 25 publications

Physiology of Microglia

Physiology of Microglia

Matrix‐degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas

Somatostatin inhibits the production of vascular endothelial growth factor in human glioma cells

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