Stimulation of cell‐surface urokinase‐type plasminogen activator activity and cell migration in vascular endothelial cells by a novel hexapeptide analogue of neurotensin

Ushiro, Shin; Mizoguchi, Kazuo; Jimi, S; Fujiwara, T.; Yoshida, Masaya; Wei, E.T.; Kitabgi, Patrick; Amagaya, Sakae; Ono, Masahiro; Kuwano, Michihiko

doi:10.1016/s0014-5793(97)01403-8

Cited by 10 publications

(6 citation statements)

References 36 publications

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“…It is the only known receptor expressed in human C13NJ microglial cells, and the effect of neurotensin on the migration of these cells is preceded by a profound modification of the F‐actin cytoskeleton, and particularly by the rapid formation of numerous cell filopodia [40], a feature also observed here in U373 glioblastoma cells treated with neurotensin. In the case of other cell types (such as T lymphocytes and leukaemic Jurkat cells) it seems that only NTR1 is responsible for cell migration [42]. The present study shows that human U373 glioblastoma cells express NTR1, NTR2 and NTR3 at least at mRNA level, an expression pattern that we also evidenced in Hs683 glioma cells (data not shown).…”

Section: Discussionsupporting

confidence: 79%

“…For example, neurotensin modulates the locomotion of the neutrophils [37], the lymphocytes [38] and the macrophages [39] that form part of the immune system, and also of microglia in the CNS [40]. Neurotensin stimulates intestinal wound healing [41] and angiogenesis [42]. It also modulates the migration features of cancer cells such as circulating malignant Sezary cells [43].…”

Section: Discussionmentioning

confidence: 99%

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The in vitro influences of neurotensin on the motility characteristics of human U373 glioblastoma cells

Servotte

Camby

Debeir

et al. 2006

Neuropathology Appl Neurobio

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Astrocytic tumours are associated with dismal prognoses due to their pronounced ability to diffusely invade the brain parenchyma. Various neuropeptides, including gastrin, are able to modulate tumour astrocyte migration. While neurotensin has been shown to influence the proliferation of glioma cells and the migratory ability of a large set of other cell types, its role in glioma cell migration has never been investigated. Neurotensin-induced modifications to the motility features of human U373 glioblastoma cells therefore constitute the topic of the present study. We evidenced that three subtypes of neurotensin receptors (NTR1, NTR2 and NTR3) are expressed in U373 glioblastoma cells, at least as far as their mRNAs are concerned. Treating U373 tumour cells with 10 nM neurotensin markedly modified the morphological patterns of these cells and also profoundly altered the organization of their actin cytoskeletons. Pull-down assays revealed that neurotensin induced the activation in U373 cells of both Racl and Cdc42 but not RhoA. Scratch wound assays evidenced that neurotensin (0.1 and 10 nM) very significantly inhibited wound colonization by U373 cells cultured in the absence of serum. In addition, quantitative phase-contrast videomicroscopy analyses showed that neurotensin decreases the motility levels of U373 glioblastoma cells when these cells are cultured on plastic. In sharp contrast, neurotensin stimulates the motility of U373 cells when they are cultured on laminin, which is a pro-adhesive extracellular matrix component ubiquitously secreted by glioma cells. Our data thus strongly suggest that, in addition to gastrin, neurotensin is a neuropeptide capable of modulating tumour astrocyte migration into the brain parenchyma.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

The in vitro influences of neurotensin on the motility characteristics of human U373 glioblastoma cells

Servotte

Camby

Debeir

et al. 2006

Neuropathology Appl Neurobio

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“…Thus NT stimulates either migration of connective and epithelial cells (Ref. 40 and Fig. 6) as well as endothelial and epithelial cell proliferation (neoangiogenesis).…”

Section: Discussionmentioning

confidence: 95%

“…6) as well as endothelial and epithelial cell proliferation (neoangiogenesis). Furthermore, NT activates proteases, such as the urokinasetype plasminogen activator involved in tissue repair (40). NT also enhances the expression of growth-related genes as well as the activity of kinases leading to proliferation of intestinal epithelial cells in vivo and in vitro (19,27,36).…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation

Brun¹,

Mastrotto²,

Beggiao³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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Because neurotensin (NT) and its highaffinity receptor (NTR1) modulate immune responses, chloride secretion, and epithelial cell proliferation, we sought to investigate their role in the repair process that follows the development of mucosal injuries during a persistent inflammation. Colonic NT and NTR1, mRNA, and protein significantly increased only after dextran sodium sulfate (DSS)-induced inflammatory damage developed. Colitis-induced body weight loss, colonic myeloperoxidase activity, and histological damage were significantly enhanced by SR-48642 administration, a nonpeptide NTR1 antagonist, whereas continuous NT infusion ameliorated colitis outcome. To evaluate the NT and NTR1 role in tissue healing, mucosal inflammatory injury was established administering 3% DSS for 5 days. After DSS discontinuation, mice rapidly gained weight, ulcers were healed, and colonic NT, NTR1, and cyclooxygenase (COX)-2 mRNA levels were upregulated, whereas SR-48642 treatment caused a further body weight loss, ulcer enlargement, and a blunted colonic COX-2 mRNA upregulation. In a woundhealing model in vitro, NT-induced cell migration in the denuded area was inhibited by indomethacin but not by an antitransforming growth factor-␤ neutralizing antibody. Furthermore, NT significantly increased COX-2 mRNA levels by 2.4-fold and stimulated PGE2 release in HT-29 cells. These findings suggest that NT and NTR1 are part of the network activated after mucosal injuries and that NT stimulates epithelial restitution at least, in part, through a COX-2 dependent pathway. neurotensin receptor type 1; healing; colitis; cyclooxygenase-2; inflammatory bowel disease INFLAMMATORY BOWEL DISEASE (IBD) is a chronic intestinal inflammatory disorder that is considered the consequence of an aberrant response of the immune system to luminal antigens (13). Although the event(s) triggering the chronic inflammatory disorder has not been identified, a variety of cells and soluble factors mediate the extended mucosal damage (13). However, after the development of mucosal injuries, the intestinal epithelium rapidly tends to reestablish its integrity (26). To reestablish mucosal integrity, epithelial cells migrate into the wounded area (epithelial restitution), and they then proliferate to replace the decreased cell pool. Studies over the past several years have shown that a variety of soluble peptides, prostaglandins, growth factors, and cytokines are secreted in a

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“…148 NT, via NTR1, binds to human umbilical vascular endothelial cells, 149 stimulating release of prostacyclin 150 and enhancing their migration, implicating a role for NT in angiogenesis. 151 A preliminary report by Castagliuolo et al 152 showed that microvascular endothelial cells in the colonic mucosa of patients with IBD express NTR1, suggesting that NT may affect endothelial cell function during intestinal inflammation.…”

Section: Nt Mediates Inflammatory Responses In the Small Intestine Anmentioning

confidence: 99%

Role of neuropeptides in inflammatory bowel disease

Gross

Pothoulakis

2007

Inflammatory Bowel Diseases

149

128

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Inflammatory bowel disease (IBD) is a chronic, relapsing condition involving complex interactions between genes and the environment. The mechanisms triggering the initial attack and relapses, however, are not well understood. In the past several years the enteric nervous system (ENS) has been implicated in the pathophysiology of IBD. Both the ENS and the central nervous system (CNS) can amplify or modulate aspects of intestinal inflammation through secretion of neuropeptides that serve as a link between the ENS and CNS. Neuropeptides are defined as any peptide released from the nervous system that serves as an intercellular signaling molecule. Neuropeptides thought to play a potentially key role in IBD include substance P, corticotropin-releasing hormone, neurotensin, vasoactive intestinal peptide, mu-opioid receptor agonists, and galanin. This review focuses on the role of these neuropeptides in the pathophysiology of IBD and discusses the cell types and mechanisms involved in this process. The available evidence that neuropeptide blockade may be considered a therapeutic approach in both Crohn's disease and ulcerative colitis will also be discussed.

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Stimulation of cell‐surface urokinase‐type plasminogen activator activity and cell migration in vascular endothelial cells by a novel hexapeptide analogue of neurotensin

Cited by 10 publications

References 36 publications

The in vitro influences of neurotensin on the motility characteristics of human U373 glioblastoma cells

The in vitro influences of neurotensin on the motility characteristics of human U373 glioblastoma cells

Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation

Role of neuropeptides in inflammatory bowel disease

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