1. Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid cells
- Author
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Guangchun Jin, Xiang Dong Yang, Walden Ai, András Falus, Govind Bhagat, Thomas G. Diacovo, Samuel Asfaha, Richard A. Friedman, Benjamin Shykind, Heuijoon Park, and Timothy C. Wang
- Subjects
Male ,Chromosomes, Artificial, Bacterial ,Skin Neoplasms ,Myeloid ,Cellular differentiation ,Green Fluorescent Proteins ,Cell ,Mice, Transgenic ,Histidine Decarboxylase ,Biology ,medicine.disease_cause ,Pediatrics ,General Biochemistry, Genetics and Molecular Biology ,Article ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,immature myeloid cells (IMCs) ,0302 clinical medicine ,Myeloid Cell Differentiation ,receptor for advanced glycation end product (RAGE) ,medicine ,Animals ,Antigens, Ly ,Transplantation, Homologous ,Genetic Predisposition to Disease ,030304 developmental biology ,Mice, Knockout ,Mice, Inbred BALB C ,0303 health sciences ,CD11b Antigen ,Cell Differentiation ,General Medicine ,Histidine decarboxylase ,histamine ,3. Good health ,tumor-associated neutrophils (TANs) ,medicine.anatomical_structure ,chemistry ,inflammation ,030220 oncology & carcinogenesis ,histidine decarboxylase (HDC) ,Colonic Neoplasms ,Immunology ,Cancer research ,Bone marrow ,Carcinogenesis ,carcinogenesis ,Histamine - Abstract
Histidine decarboxylase (HDC), the unique enzyme responsible for histamine generation, is highly expressed in myeloid cells, but its function in these cells is poorly understood. Here we show that Hdc-knockout mice show a high rate of colon and skin carcinogenesis. Using Hdc-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the Hdc promoter, we show that Hdc is expressed primarily in CD11b +Ly6G+ immature myeloid cells (IMCs) that are recruited early on in chemical carcinogenesis. Transplant of Hdc-deficient bone marrow to wild-type recipients results in increased CD11b + Ly6G + cell mobilization and reproduces the cancer susceptibility phenotype of Hdc-knockout mice. In addition, Hdc-deficient IMCs promote the growth of tumor allografts, whereas mouse CT26 colon cancer cells downregulate Hdc expression through promoter hypermethylation and inhibit myeloid cell maturation. Exogenous histamine induces the differentiation of IMCs and suppresses their ability to support the growth of tumor allografts. These data indicate key roles for Hdc and histamine in myeloid cell differentiation and CD11b+Ly6G+IMCs in early cancer development. © 2011 Nature America, Inc. All rights reserved.
- Published
- 2010