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Immunology

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

Zoltán Pós, Géza Sáfrány, Kerstin Müller, Sára Tóth, András Falus and Hargita Hegyesi
Zoltán Pós
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Géza Sáfrány
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Kerstin Müller
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Sára Tóth
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András Falus
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Hargita Hegyesi
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DOI: 10.1158/0008-5472.CAN-05-0011 Published May 2005
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Abstract

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.

  • Melanoma
  • Histamine
  • Histidine decarboxylase
  • Inflammation
  • Murine model

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received January 4, 2005.
  • Revision received February 17, 2005.
  • Accepted March 9, 2005.
  • ©2005 American Association for Cancer Research.
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Cancer Research: 65 (10)
May 2005
Volume 65, Issue 10
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Phenotypic Profiling of Engineered Mouse Melanomas with Manipulated Histamine Production Identifies Histamine H2 Receptor and Rho-C as Histamine-Regulated Melanoma Progression Markers
Zoltán Pós, Géza Sáfrány, Kerstin Müller, Sára Tóth, András Falus and Hargita Hegyesi
Cancer Res May 15 2005 (65) (10) 4458-4466; DOI: 10.1158/0008-5472.CAN-05-0011

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Phenotypic Profiling of Engineered Mouse Melanomas with Manipulated Histamine Production Identifies Histamine H2 Receptor and Rho-C as Histamine-Regulated Melanoma Progression Markers
Zoltán Pós, Géza Sáfrány, Kerstin Müller, Sára Tóth, András Falus and Hargita Hegyesi
Cancer Res May 15 2005 (65) (10) 4458-4466; DOI: 10.1158/0008-5472.CAN-05-0011
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Cancer Research Online ISSN: 1538-7445
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