Serotonin and Dopamine Receptor Expression in Solid Tumours Including Rare Cancers

Peters, Marloes A M; Meijer, Coby; Fehrmann, Rudolf S.N.; Walenkamp, Annemiek; Kema, Ido P.; Vries, Elisabeth G.E. de; Hollema, Harry; Oosting, Sjoukje F.

doi:10.1007/s12253-019-00734-w

Cited by 39 publications

(36 citation statements)

References 26 publications

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“…Existing studies had shown that HTR1B indeed had close relationship with malignant tumor.A stduy result demonstrated that 5-HTR1B, 5-HTR2B, DRD1, and DRD2 showed mRNA overexpression in a broad spectrum of common and rare cancers. 13 To obtain the recurrence risk model that identifies patients at low and high risk for recurrence, a other study was constructed, followed by the validation of its performance in the validation set and a microarray dataset. Totally, 378 differentially expressed genes(DEGs), including 20 recurrence-associated DEGs were identified between the recurrent and non-recurrent tumors in the training set.…”

Section: Discussionmentioning

confidence: 99%

Effect of Wumei Decoction on Core Signal Transduction Molecules of Microenvironment in Lung Metastasis of Breast Cancer

wang

et al. 2020

Preprint

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Background The influence of traditional Chinese medicine on the tumor microenvironment is one of the mechanisms of its overall conditioning effect. In this study, we observed the influence of Wumei decoction,a traditional Chinese medicine classic prescription, on the core signal transduction molecules of the lung metastasis microenvironment in the model of lung metastasis of breast cancer in mice. Methods A breast cancer animal model established by inoculating the second pair of mammary fat pads of SPF grade Balb/c female mice with mouse breast cancer 4T1 cells, stably transduced luciferase. Model animals were divided into drug observation group, drug control group and blank control group. Bioluminescence imaging technique in vivo was used to observe the growth and metastasis of breast cancer in situ and lung. The gene expression in the lung metastasis microenvironment of the drug observation group and the blank control group was detected by Agilent expression profiling chip, and the differential genes were screened. And STRING (https://string-db.org/) online analysis system was used to obtain the signal transduction network, and then the MCODE plug-in of Cytosacpe software was used to obtain the core signal transduction molecule. Finally, the expression of these signal transduction molecules was detected by RT-PCR, immunohistochemistry and Western blot. Results Observed from the bioluminescence imaging technology in vivo, the fluorescent area of the breast cancer in inoculation area of each group mice gradually increased over time, indicating that the tumor volume is continuously increasing. The fluorescence distribution of the blank control group was dispersed on the 30th day, which had exceeded the vicinity of the original inoculation focus, indicating that the tumor had obvious metastasis. However, the drug observation group and the drug control group did not show such obvious transfer. Transcription expression profile chip results showed that there were 123 differentially expressed genes in the drug observation group and the blank control group, of which 64 genes were up-regulated and 59 genes were down-regulated. The signal transduction network of the 123 differentially expressed genes was obtained. The core genes recommended were AGT, CCL20, CXCL9, CXCL10, and HTR1B. RT-PCR results showed that the expression of AGT, CCL20, CXCL9, CXCL10, and HTR1B in the drug observation group were reduced compared with the blank control group, and the difference was statistically significant, p < 0.01. The results of immunohistochemistry showed that the core genes of the drug observation group showed a low expression trend, and the difference of CCL20 and CXCL10 was statistically significant, p < 0.01. Western blotting results also showed that each core gene protein in the drug observation group, compared with the blank control group, showed a downward trend. The difference of AGT and CCL20 was statistically significant, p < 0.01, and the difference of CXCL10 was also statistically significant, p < 0.05 . Conclusions Wumei decoction,a traditional Chinese medicine classic prescription, can inhibit lung metastasis of breast cancer to a certain extent. Inhibiting the expression of AGT, CCL20, CXCL9, CXCL10, HTR1B and other core signal transduction molecules in the lung metastasis microenvironment is one of its mechanisms.

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Section: Discussionmentioning

confidence: 99%

Effect of Wumei Decoction on Core Signal Transduction Molecules of Microenvironment in Lung Metastasis of Breast Cancer

wang

et al. 2020

Preprint

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“…In addition, it was discovered that there are many kinds of 5-HTR subtypes on a variety of cancers, including PC (32), HCC (33–35), CRC (36) etc. 5-HT could promote the development and progression of these cancers by activating the 5-HTR subtypes, such as 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B (44, 99). 5-HT1B was overexpressed in human NPC samples (44), which reminded us that the elevated 5-HT in plasma in NPC could promote the progression of NPC through 5-HTR.…”

Section: Discussionmentioning

confidence: 99%

“…5-HT could promote the development and progression of these cancers by activating the 5-HTR subtypes, such as 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B (44, 99). 5-HT1B was overexpressed in human NPC samples (44), which reminded us that the elevated 5-HT in plasma in NPC could promote the progression of NPC through 5-HTR. These findings suggest that the significantly elevated C. ramosum in the intestinal flora of NPC patients may affect the development and progression of NPC through increasing the 5-HT levels in the blood.…”

Section: Discussionmentioning

confidence: 99%

“…A variety of researches have found that 5-HT can stimulate the development and progression of multifarious cancers, such as prostate carcinoma (PC) (32), hepatocellular carcinoma (HCC) (33–35), CRC (36), small-cell lung cancer (SCLC) (37), pancreatic ductal adenocarcinoma (PDAC) (38, 39), cholanfiocarcinoma (40), breast cancer (41), ovary carcinoma (42), and glioma (43) and carcinoids (31) through the 5-HT receptor (5-HTR) subtypes like 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B etc. What interested us most is that a study has found that 5-HT1B was overexpressed in human NPC samples (44), which reminds us that 5-HT may play a crucial role in NPC development. This has aroused our great interest in research.…”

Section: Introductionmentioning

confidence: 99%

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Intestinal Flora Disruption and Novel Biomarkers Associated With Nasopharyngeal Carcinoma

Jiang

Zhang

et al. 2019

Front. Oncol.

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Background: Nasopharyngeal carcinoma (NPC) is a malignant nasopharyngeal disease with a complicated etiology that occurs mostly in southern China. Intestinal flora imbalance is believed to be associated with a variety of organ malignancies. Current studies revealed that the destruction of intestinal flora is associated with NPC, and many studies have shown that intestinal flora can be used as a biomarker for many cancers and to predict cancer.Methods: To compare the differences in intestinal flora compositions and biological functions among 8 patients with familial NPC (NPC_F), 24 patients with sporadic NPC (NPC_S), and 27 healthy controls (NOR), we compared the intestinal flora DNA sequencing and hematological testing results between every two groups using bioinformatic methods.Results: Compared to the NOR group, the intestinal flora structures of the patients in the NPC_F and NPC_S groups showed significant changes. In NPC_F, Clostridium ramosum, Citrobacter spp., Veillonella spp., and Prevotella spp. were significantly increased, and Akkermansia muciniphila and Roseburia spp. were significantly reduced. In NPC_S, C. ramosum, Veillonella parvula, Veillonella dispar, and Klebsiella spp. were significantly increased, and Bifidobacterium adolescentis was significantly reduced. A beta diversity analysis showed significant difference compared NPC_F with NOR based on Bray Curtis (P = 0.012) and Unweighted UniFrac (P = 0.0045) index, respectively. The areas under the ROC curves plotted were all 1. Additionally, the concentrations of 5-hydroxytryptamine (5-HT) in NPC_F and NPC_S were significantly higher than those of NOR. C. ramosum was positively correlated with 5-HT (rcm: 0.85, P < 0.001). A functional analysis of the intestinal flora showed that NPC_F was associated with Neurodegenerative Diseases (P = 0.023) and that NPC_S was associated with Neurodegenerative Diseases (P = 0.045) as well.Conclusion: We found that NPC was associated with structural imbalances in the intestinal flora, with C. ramosum that promoted the elevation of 5-HT and opportunistic pathogens being significantly increased, while probiotics significantly decreased. C. ramosum can be used as a novel biomarker and disease prediction models should be established for NPC. The new biomarkers and disease prediction models may be used for disease risk prediction and the screening of high-risk populations, as well as for the early noninvasive diagnosis of NPC.

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“…Another hypothesis is that serotonin’s mitogenic effect is dose-dependent, where higher doses promote cell proliferation and lower doses cause vasoconstriction on tumor vessels, leading to inhibition of tumor growth. By contrast, several genetic studies have shown a decreased 5-hydroxytryptamine receptor 1B gene (HTR1B) in the lung, renal, osteosarcoma, and non-Hodgkin’s lymphoma, suggesting that serotonin may behave as a tumor suppressor when it interacts with 5-HTB receptor subtypes [ 49 ].…”

Section: Serotonin Pathway As a Potential Therapeutic Targetmentioning

confidence: 99%

Serotonin Pathway in Cancer

Balakrishna

George

Hatoum

et al. 2021

IJMS

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Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine produced from the essential amino acid tryptophan. Serotonin’s role as a neurotransmitter in the central nervous system and a motility mediator in the gastrointestinal tract has been well defined, and its function in tumorigenesis in various cancers (gliomas, carcinoids, and carcinomas) is being studied. Many studies have shown a potential stimulatory effect of serotonin on cancer cell proliferation, invasion, dissemination, and tumor angiogenesis. Although the underlying mechanism is complex, it is proposed that serotonin levels in the tumor and its interaction with specific receptor subtypes are associated with disease progression. This review article describes serotonin’s role in cancer pathogenesis and the utility of the serotonin pathway as a potential therapeutic target in cancer treatment. Octreotide, an inhibitor of serotonin release, is used in well-differentiated neuroendocrine cancers, and the tryptophan hydroxylase (TPH) inhibitor, telotristat, is currently being investigated in clinical trials to treat patients with metastatic neuroendocrine tumors and advanced cholangiocarcinoma. Several in vitro studies have shown the anticancer effect of 5-HT receptor antagonists in various cancers such as prostate cancer, breast cancer, urinary bladder, colorectal cancer, carcinoid, and small-cell lung cancer. More in vivo studies are needed to assess serotonin’s role in cancer and its potential use as an anticancer therapeutic target. Serotonin is also being evaluated for its immunoregulatory properties, and studies have shown its potential anti-inflammatory effect. Therefore, it would be of interest to explore the combination of serotonin antagonists with immunotherapy in the future.

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Serotonin and Dopamine Receptor Expression in Solid Tumours Including Rare Cancers

Cited by 39 publications

References 26 publications

Effect of Wumei Decoction on Core Signal Transduction Molecules of Microenvironment in Lung Metastasis of Breast Cancer

Effect of Wumei Decoction on Core Signal Transduction Molecules of Microenvironment in Lung Metastasis of Breast Cancer

Intestinal Flora Disruption and Novel Biomarkers Associated With Nasopharyngeal Carcinoma

Serotonin Pathway in Cancer

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