Serotonin and ionizing radiation synergistically affect proliferation and adhesion molecule expression of malignant melanoma cells

Müller, Kerstin; Gilbertz, Klaus-Peter; Meineke, Viktor

doi:10.1016/j.jdermsci.2012.08.001

Cited by 13 publications

(12 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increment in the concentration of 5-HT is known to exhibit a pro-mitogenic effect in cancers 4 , 5 , 35 , while some studies describe a significant reduction in the kinetics of serotonin uptake by platelets in some cancers 15 , 16 . Intriguingly, there are several reports, which found, even if not unequivocally, that using 5-HT or serotonergic agonists can be implemented in tumor growth inhibition 16 , 36 , 37 . From these diverging opinions, it makes sense to argue that based on the tumor type, associated events, the dose and the receptors involved, 5-HT might hinder the process of tumor growth; a great deal of revised evidence will be needed before we can know how this mechanism actually ensues.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early Hepatocellular Carcinoma Recurrence?

et al. 2017

View full text Add to dashboard Cite

Purpose: Serotonin (5-hydroxytryptamine, 5-HT) is well known for its growth stimulatory effect on several types of carcinoma and tumor cells. Since a large portion of 5-HT is stored and transported by platelets, the aim of this study was to assess the influence of platelet-sequestered 5-HT on post-resection hepatocellular carcinoma (HCC) recurrence.Methods: This pilot study was conducted in a cohort of forty patients diagnosed with HCC undergoing partial hepatectomy. 5-HT levels in serum, plasma and intra-platelet (IP) were monitored preoperatively and four weeks after liver resection. The patients were followed every three months after the surgery.Results: Follow-up was standardized to a fixed length of time. Fifteen patients (37.5%) developed HCC recurrence during 18 months follow-up. Patients with recurrence had significantly reduced serum and IP 5-HT levels at four weeks of liver resection (P = 0.003 and P = 0.014 respectively). Accordingly, in the Cox regression hazard model, serum and IP 5-HT were able to independently predict the recurrence (hazard ratio = 0.1, 95% confidence interval = 0.01 - 0.75 and hazard ratio = 0.1, 95% confidence interval = 0.01 - 0.89 respectively). The optimal cut-off value of 42.77 ng/ml for serum [area under the curve (AUC): 0.78, P = 0.003] and 0.3117 ng per 106 platelets (AUC: 0.733, P = 0.015), on receiver operating characteristic (ROC) curve corresponded to maximum sensitivity and specificity of prediction. The disease free interval was significantly worse in patients with low serum and IP 5-HT (P = 0.001 and P = 0.029 respectively).Conclusion: IP 5-HT monitored during early follow-up, after liver resection may represent a useful marker of early HCC recurrence.

show abstract

Section: Discussionmentioning

confidence: 99%

“…5-HT has also been proposed as a diagnostic marker of HCC 14 . Concurrently, a diametrically opposite effect of 5-HT has been reported on its tumor inhibitory properties; a substantial exhaustion in the platelet uptake of 5-HT is evidently observed in clinical and translational studies 15 , 16 .…”

Section: Introductionmentioning

confidence: 99%

Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early Hepatocellular Carcinoma Recurrence?

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Two in vitro studies evaluated the effect of serotonin on melanoma growth with opposite results. Serotonin inhibited proliferation of 5-HTR2B expressing human melanoma cell line IPC298 but it did not affect B16F0 murine melanoma cell proliferation, in which however, receptor expression was not assessed [5,20]. On the other hand, mice with serotonin depletion due to knockout of a serotonin transporter had smaller B16F0 murine melanomas than mice with a functional serotonin transporter and thus unaffected serotonin concentrations in blood [5].…”

Section: Discussionmentioning

confidence: 90%

Serotonin and Dopamine Receptor Expression in Solid Tumours Including Rare Cancers

Peters

Meijer

Fehrmann

et al. 2019

Pathol. Oncol. Res.

View full text Add to dashboard Cite

In preclinical studies serotonin stimulates and dopamine inhibits tumour growth and angiogenesis. Information regarding serotonin and dopamine receptor (5-HTR and DRD) expression in human cancers is limited. Therefore, we screened a large tumour set for receptor mRNA overexpression using functional genomic mRNA (FGmRNA) profiling, and we analysed protein expression and location of 5-HTR1B, 5-HTR2B, DRD1, and DRD2 with immunohistochemistry in different tumour types. With FGmRNA profiling 11,756 samples representing 43 tumour types were compared to 3,520 normal tissue samples to analyse receptor overexpression. 5-HTR2B overexpression was present in many tumour types, most frequently in uveal melanomas (56%). Receptor overexpression in rare cancers included 5-HTR1B in nasopharyngeal carcinoma (17%), DRD1 in ependymoma (30%) and synovial sarcoma (21%), and DRD2 in astrocytoma (13%). Immunohistochemistry demonstrated high 5-HTR2B protein expression on melanoma and gastro-intestinal stromal tumour cells and endothelial cells of colon, ovarian, breast, renal and pancreatic tumours. 5-HTR1B expression was predominantly low. High DRD2 protein expression on tumour cells was observed in 48% of pheochromocytomas, and DRD1 expression ranged from 14% in melanoma to 57% in renal cell carcinoma.In conclusion, 5-HTR1B, 5-HTR2B, DRD1, and DRD2 show mRNA overexpression in a broad spectrum of common and rare cancers. 5-HTR2B protein is frequently highly expressed in human cancers, especially on endothelial cells. These findings support further investigation of especially 5HTR2B as a potential treatment target.

show abstract

“…Serotonin, a monoamine synthesized by enterochromaffin cells in the intestinal mucosa, is largely (about 95%) sequestered by platelets in dense granules, from which it is released in response to various stimuli [12]. A large body of experimental data support both stimulatory and inhibitory properties of serotonin on tumor onset and progression [129][130][131][132][133][134]. Such different behavior is much likely due to the ability of serotonin to act in a concentration-dependent manner, as well as in its capability to activate distinct signaling pathways, depending on the receptor subtype present at various tumor stages.…”

Section: Platelet-derived Bioactive Compoundsmentioning

confidence: 99%

The “Janus Face” of Platelets in Cancer

Catani

Savini

Tullio

et al. 2020

IJMS

View full text Add to dashboard Cite

Besides their vital role in hemostasis and thrombosis, platelets are also recognized to be involved in cancer, where they play an unexpected central role: They actively influence cancer cell behavior, but, on the other hand, platelet physiology and phenotype are impacted by tumor cells. The existence of this platelet-cancer loop is supported by a large number of experimental and human studies reporting an association between alterations in platelet number and functions and cancer, often in a way dependent on patient, cancer type and treatment. Herein, we shall report on an update on platelet-cancer relationships, with a particular emphasis on how platelets might exert either a protective or a deleterious action in all steps of cancer progression. To this end, we will describe the impact of (i) platelet count, (ii) bioactive molecules secreted upon platelet activation, and (iii) microvesicle-derived miRNAs on cancer behavior. Potential explanations of conflicting results are also reported: Both intrinsic (heterogeneity in platelet-derived bioactive molecules with either inhibitory or stimulatory properties; features of cancer cell types, such as aggressiveness and/or tumour stage) and extrinsic (heterogeneous characteristics of cancer patients, study design and sample preparation) factors, together with other confounding elements, contribute to “the Janus face” of platelets in cancer. Given the difficulty to establish the univocal role of platelets in a tumor, a better understanding of their exact contribution is warranted, in order to identify an efficient therapeutic strategy for cancer management, as well as for better prevention, screening and risk assessment protocols.

show abstract

Serotonin and ionizing radiation synergistically affect proliferation and adhesion molecule expression of malignant melanoma cells

Cited by 13 publications

References 58 publications

Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early Hepatocellular Carcinoma Recurrence?

Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early Hepatocellular Carcinoma Recurrence?

Serotonin and Dopamine Receptor Expression in Solid Tumours Including Rare Cancers

The “Janus Face” of Platelets in Cancer

Contact Info

Product

Resources

About