Endocannabinoid system regulates migration of endometrial stromal cells via cannabinoid receptor 1 through the activation of PI3K and ERK1/2 pathways

Gentilini, Davide; Besana, Alessandra; Viganò, Paola; Dalino, Paolo; Vignali, Michele; Melandri, Michela; Busacca, Mauro; Blasio, Anna Maria Di

doi:10.1016/j.fertnstert.2010.02.006

Cited by 39 publications

(32 citation statements)

References 29 publications

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“…[33][34][35] The application of a CB1 agonist led to a migratory phenotype, characterized by a rapid F-actin degradation, more stress fibers and a localization of F-actin at the edge of endometrial stromal cells. 36 Our experiments validated these results for tumor cells by measuring the undirected migration speed of single cells that were altered by cannabinoids. Thereby we observed contrary effects after the application of the CB1 agonist that might be cell line specific.…”

Section: Cannabinoids Change the Cell Motility And Affect The Cell Arsupporting

confidence: 65%

The influence of biomechanical properties and cannabinoids on tumor invasion

Hohmann

Grabiec

Ghadban

et al. 2016

Cell Adhesion & Migration

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Background: Cannabinoids are known to have an anti-tumorous effect, but the underlying mechanisms are only sparsely understood. Mechanical characteristics of tumor cells represent a promising marker to distinguish between tumor cells and the healthy tissue. We tested the hypothesis whether cannabinoids influence the tumor cell specific mechanical and migratory properties and if these factors are a prognostic marker for the invasiveness of tumor cells.Methods: 3 different glioblastoma cell lines were treated with cannabinoids and changes of mechanical and migratory properties of single cells were measured using atomic force microscopy and time lapse imaging. The invasiveness of cell lines was determined using a co-culture model with organotypic hippocampal slice cultures.Results: We found that cannabinoids are capable of influencing migratory and mechanical properties in a cell line specific manner. A network analysis revealed a correlation between a "generalized stiffness" and the invasiveness for all tumor cell lines after 3 and 4 d of invasion time: Conclusions: Here we could show that a "generalized stiffness" is a profound marker for the invasiveness of a tumor cell population in our model and thus might be of high clinical relevance for drug testing. Additionally cannabinoids were shown to be of potential use for therapeutic approaches of glioblastoma.

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Section: Cannabinoids Change the Cell Motility And Affect The Cell Arsupporting

confidence: 65%

The influence of biomechanical properties and cannabinoids on tumor invasion

Hohmann

Grabiec

Ghadban

et al. 2016

Cell Adhesion & Migration

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“…These events are mainly regulated by steroid hormones, the timing and concentrations of which dictate the balance between endometrial growth and transformation (Guzeloglu-Kayisli et al 2004). Interestingly, recent data support the idea that the endocannabinoid system plays an important role in the control of endometrial plasticity by regulating endometrial cell motility (Gentilini et al 2010). We demonstrated for the first time that methanandamide stimulates endometrial stromal cell migration in a dose-dependent manner (Fig.…”

Section: Endocannabinoid and The Uterussupporting

confidence: 63%

“…This phenotype is characterised by the rapid dissolution of F-actin stress fibres, progressive localisation of F-actin towards the edge of the cell membrane and by the presence of numerous stress fibre arcs ( Fig. 3; Hotulainen & Lappalainen 2006, Gentilini et al 2010). In addition, we also showed that methanandamide can regulate endometrial stromal cell motility by increasing electrical signal generated by K C channels that is an essential component of cellular migration.…”

Section: Endocannabinoid and The Uterusmentioning

confidence: 99%

The endocannabinoid pathway and the female reproductive organs

Blasio¹,

Vignali²,

Gentilini³

2012

Journal of Molecular Endocrinology

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Endocannabinoids are endogenous ligands of cannabinoid, vanilloid and peroxisome proliferator-activated receptors that activate multiple signal transduction pathways. Together with their receptor and the enzymes responsible for their synthesis and degradation, these compounds constitute the endocannabinoid system that has been recently shown to play, in humans, an important role in modulating several central and peripheral functions including reproduction. Given the relevance of the system, drugs that are able to interfere with the activity of endocannabinoids are currently considered as candidates for the treatment of various diseases. In this review, we will summarise the current knowledge regarding the effects of endocannabinoids in female reproductive organs. In particular, we will focus on some newly reported mechanisms that can affect endometrial plasticity both in physiological and in pathological conditions.

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“…Increased estrogen synthesis in endometriosis lesions makes those results comparable to these data. Furthermore, the TRP agonist endocannabinoids regulate the migration of endometrial stromal cells (Gentilini et al 2010). TRPA1/TRPV1 in non-neural cells (stromal, glandular and epithelial cells) might have estrogen-mediated normal sensory, secretory and consequent inflammation-generating and pain-transmitting roles under pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

Pohóczky

Kun

Szalontai

et al. 2015

Journal of Molecular Endocrinology

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Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors expressed predominantly in sensory nerves are activated by inflammatory stimuli and mediate inflammation and pain. Although they have been shown in the human endometrium, their regulation and function are unknown. Therefore, we investigated their estrogen-and progesterone-dependent alterations in the rat endometrium in comparison with the estrogenregulated inflammatory cytokine macrophage migration inhibitory factor (MIF). Four-week-old (sexually immature) and four-month-old (sexually mature) female rats were treated with the non-selective estrogen receptor (ER) agonist diethylstilboestrol (DES), progesterone and their combination, or ovariectomized. RT-PCR and immunohistochemistry were performed to determine mRNA and protein expression levels respectively. Channel function was investigated with ratiometric [Ca 2C ] i measurement in cultured primary rat endometrial cells. Both TRP receptors and MIF were detected in the endometrium at mRNA and protein levels, and their localizations were similar. Immunostaining was observed in the immature epithelium, while stromal, glandular and epithelial positivity were observed in adults. Functionally active TRP receptor proteins were shown in endometrial cells by activation-induced calcium influx. In adults, Trpa1 and Trpv1 mRNA levels were significantly up-regulated after DES treatment. TRPA1 increased after every treatment, but TRPV1 remained unchanged following the combined treatment and ovariectomy. In immature rats, DES treatment resulted in increased mRNA expression of both channels and elevated TRPV1 immunopositivity. MIF expression changed in parallel with TRPA1/TRPV1 in most cases. DES up-regulated Trpa1, Trpv1 and Mif mRNA levels in endometrial cell cultures, but 17b-oestradiol having ERa-selective potency increased only the expression of Trpv1. We provide the first evidence for TRPA1/TRPV1 expression and their estrogen-induced up-regulation in the rat endometrium in correlation with the MIF. Journal of Molecular EndocrinologyResearch K POHÓ CZKY and others TRPV1 and TRPA1 in the rat endometrium 56:2 135-149

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Endocannabinoid system regulates migration of endometrial stromal cells via cannabinoid receptor 1 through the activation of PI3K and ERK1/2 pathways

Cited by 39 publications

References 29 publications

The influence of biomechanical properties and cannabinoids on tumor invasion

The influence of biomechanical properties and cannabinoids on tumor invasion

The endocannabinoid pathway and the female reproductive organs

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

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