Suppression of Melanoma Cell Proliferation by Histidine Decarboxylase Specific Antisense Oligonucleotides

Hegyesi, Hargita; Somlai, Beáta; Varga, Valeria Lia; Tóth, Gabriella; Kovács, P.; Molnár, Eszter; László, Valéria; Kárpáti, Sarolta; Rivera, Elena; Falus, András; Darvas, Zsuzsanna

doi:10.1046/j.0022-202x.2001.01406.x

Cited by 59 publications

(38 citation statements)

References 16 publications

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“…Therefore, histidine decarboxylase can serve as a specific marker for biosynthesis of histamine. It has been shown that levels of mRNA encoding histidine decarboxylase, histidine decarboxylase protein expression, and enzymatic activity are significantly increased in both experimental and human tumors, such as melanoma (3,4), small cell lung carcinoma (5), breast carcinoma (6), endometrial cancer (7), and colorectal carcinoma (8). These data suggest that histamine may be directly involved in tumor development and progression.…”

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confidence: 74%

The Role of Cyclooxygenase-2 in Mediating the Effects of Histamine on Cell Proliferation and Vascular Endothelial Growth Factor Production in Colorectal Cancer

Cianchi

Cortesini

Schiavone³

et al. 2005

Clinical Cancer Research

103

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Purpose: Activity of histidine decarboxylase, the key enzyme in the synthesis of histamine, has been shown to be increased in several types of human tumors.We attempted to establish whether the possible involvement of histidine decarboxylase and histamine in colorectal carcinogenesis might be mediated by the activation of the cyclooxygenase-2 (COX-2) pathway. Experimental Design: Expression/activity of histidine decarboxylase, histamine content, and prostaglandin E 2 (PGE 2 ) production were analyzed in 33 colorectal cancer samples and in the HT29, Caco-2, and HCT116 colon cancer cell lines. The effects of histamine, celecoxib, and H 1 , H 2 , and H 4 receptor antagonists on COX-2 expression/activity, cell proliferation, and vascular endothelial growth factor (VEGF) production were assessed in the three colon cancer lines that showed different constitutive COX-2 expression. Results: We showed the up-regulation of histidine decarboxylase protein expression and activity in the tumor specimens when compared with normal colonic mucosa. Histidine decarboxylase activity and histamine content were also significantly higher in metastatic tumors than in nonmetastatic ones.These variables significantly correlated with tumor PGE 2 production.The administration of histamine increased COX-2 expression/activity, cell proliferation, and VEGF production in the COX-2-positive HT29 and Caco-2 cells. Treatment with either H 2 /H 4 receptor antagonists or celecoxib prevented these effects. Histamine had no effect on both the COX-2 pathway andVEGF production in the COX-2-negative HCT116 cells. Conclusions: Our data showed that histamine exerts both a proproliferative and a proangiogenic effect via H 2 /H 4 receptor activation. These effects are likely to be mediated by increasing COX-2-related PGE 2 production in COX-2-expressing colon cancer cells.

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confidence: 74%

The Role of Cyclooxygenase-2 in Mediating the Effects of Histamine on Cell Proliferation and Vascular Endothelial Growth Factor Production in Colorectal Cancer

Cianchi

Cortesini

Schiavone³

et al. 2005

Clinical Cancer Research

103

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“…As melanoma tumors are known to overexpress HDC, thereby releasing large amounts of histamine, an inflammatory mediator in their microenvironment, the clarification of the consequences of this phenomenon is of imperative importance. Although in previous in vitro studies, we and others have repeatedly suggested a possible involvement of neoplastic histamine secretion in melanoma tumor progression (15,(27)(28)(29), there were only sparse in vivo data available, providing rather indirect evidence for this concept (30).…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Profiling of Engineered Mouse Melanomas with Manipulated Histamine Production Identifies Histamine H2 Receptor and Rho-C as Histamine-Regulated Melanoma Progression Markers

Pós

Sáfrány

Müller³

et al. 2005

Cancer Research

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In the present study, the impact of acquired neoplastic L-histidine decarboxylase (HDC) expression, and its direct consequence, the release of histamine in the tumor environment, was assessed on melanoma tumor progression. B16-F10 mouse melanoma cells were manipulated via stable transfection, and nine novel transgenic variants were generated in triplicates, constitutively expressing the full-length sense mouse HDC mRNA, a mock control, and an antisense HDC RNA segment, respectively. Establishing both primary skin tumors and lung metastases in C57BL/6 mice, the nine variants with different histamine-releasing capacities were subjected to a comprehensive comparative progression profiling in vivo. Our analyses showed trends of markedly accelerated tumor growth (P < 0.001), and moderately increased metastatic colony-forming potential (P = 0.010) along with rising levels of local histamine production. Using RNase protection assay for screening of the melanoma progression profile, and Western blotting for subsequent result validation, we looked for molecular progression markers affected by melanoma histamine secretion. Investigation of 21 functionally clustered markers associated with tumor proliferation, angiogenesis, invasivity, metastasis formation, local or systemic immunomodulation, and histamine signaling revealed positive correlations between histamine production, tumor histamine H2 receptor and rho-C expression (P < 0.001, P = 0.002, respectively). These observations confirm the involvement of histamine in the molecular machinery of melanoma progression. (Cancer Res 2005; 65(10): 4458-66)

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“…The mast cell-derived mediators, such as histamine, tryptase, bFGF, VEGF, and IL-8, are shown to enhance tumor growth and angiogenesis. The studies have shown that an inhibition of histidine decarboxylase, a key enzyme involved in histamine synthesis, is associated with attenuation of cancer proliferation (Hegyesi et al 2001) and thus suggesting that histamine acts as an autocrine growth factor to regulate the cell proliferation (Lampiasi et al 2007). In lung adenocarcinoma, the number of mast cells has been directly correlated with tumor angiogenesis and poor prognosis (Ch'ng et al 2006;Imada et al 2000).…”

Section: Cancermentioning

confidence: 98%

Mast cells: an expanding pathophysiological role from allergy to other disorders

Anand

Singh

Jaggi

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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The mast cells are multi-effector cells with wide distribution in the different body parts and traditionally their role has been well-defined in the development of IgE-mediated hypersensitivity reactions including bronchial asthma. Due to the availability of genetically modified mast cell-deficient mice, the broadened pathophysiological role of mast cells in diverse diseases has been revealed. Mast cells exert different physiological and pathophysiological roles by secreting their granular contents, including vasoactive amines, cytokines and chemokines, and various proteases, including tryptase and chymase. Furthermore, mast cells also synthesize plasma membrane-derived lipid mediators, including prostaglandins and leukotrienes, to produce diverse biological actions. The present review discusses the pathophysiological role of mast cells in different diseases, including atherosclerosis, pulmonary hypertension, ischemia-reperfusion injury, male infertility, autoimmune disorders such as rheumatoid arthritis and multiple sclerosis, bladder pain syndrome (interstitial cystitis), anxiety, Alzheimer's disease, nociception, obesity and diabetes mellitus.

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Suppression of Melanoma Cell Proliferation by Histidine Decarboxylase Specific Antisense Oligonucleotides

Cited by 59 publications

References 16 publications

The Role of Cyclooxygenase-2 in Mediating the Effects of Histamine on Cell Proliferation and Vascular Endothelial Growth Factor Production in Colorectal Cancer

The Role of Cyclooxygenase-2 in Mediating the Effects of Histamine on Cell Proliferation and Vascular Endothelial Growth Factor Production in Colorectal Cancer

Phenotypic Profiling of Engineered Mouse Melanomas with Manipulated Histamine Production Identifies Histamine H2 Receptor and Rho-C as Histamine-Regulated Melanoma Progression Markers

Mast cells: an expanding pathophysiological role from allergy to other disorders

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