Histamine content in colorectal cancer. Are there sufficient levels of histamine to affect lymphocyte function?

Reynolds, Jeffrey; Akhter, Javed; Adams, Warwick J.; Dl, Morris

doi:10.1016/s0748-7983(97)92388-x

Cited by 27 publications

(27 citation statements)

References 18 publications

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“…25 A downregulation in endothelial P-selectin expression may therefore result in the recruitment of fewer, growth factor producing, leukocytes and in a less growth stimulating microenvironment for the tumor cells. [26][27][28] However, our results demonstrate that, compared to patients with liver metastases, in patients without any metastases a high expression level of endothelial P-selectin was maintained, and that this is accompanied by high numbers of infiltrating leukocytes. As tumors without metastases generally have a less infiltrating character and a better prognosis, we suggest that the latter mechanism, that is, tumor growth promotion by infiltrating cells, is less likely to occur.…”

Section: Discussionmentioning

confidence: 87%

Progressive loss of endothelial P-selectin expression with increasing malignancy in colorectal cancer

Peeters

Ruers

Westphal

et al. 2005

Laboratory Investigation

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Adhesion of inflammatory cells to vascular endothelium is mediated by specific cell adhesion receptors on both leukocytes and endothelial cells. One of the adhesion molecules on the endothelium is P-selectin. Decreased vascular P-selectin expression has been associated with tumor progression in melanoma patients. We now report on the expression of endothelial P-selectin in colorectal cancer (CRC). We studied a colorectal tissue specimen series ranging from normal colorectal tissue via unmetastasized primary tumors to tumors with the same depth of invasion at the primary site but with liver metastases. Moreover, P-selectin expression levels in liver metastases were determined. The number of P-selectin positive vessels as a fraction of the total number of vessels, both intra-and peritumorally, was determined by staining for CD62P and CD34, respectively. Furthermore, by immunostaining for leukocytes (CD45) and macrophages (CD68), it was evaluated whether levels of P-selectin expression influenced infiltrate density and composition. The results showed that levels of peritumoral P-selectin expression were reciprocal to the degree of progression in CRC. This relation was even more pronounced intratumorally: in metastasized primary tumors and in the metastatic lesions, P-selectin expression was virtually absent. This distribution pattern was reflected in the numbers of leukocytes that accumulated in the various tissues, since in the primary tumors with metastases, and in the metastatic lesions, hardly any infiltrating cells were observed. In these lesions, leukocytes were present in the peritumoral zone, but seemed unable to enter the tumor tissue. In primary tumors without metastasis, the intratumoral leukocyte infiltration density was significantly higher. Recruitment levels of macrophages remained constant throughout the different tissues. We suggest that downregulation of endothelial P-selectin expression is a mechanism by which CRC lesions evade inflammatory regression and, thereby, progress to a more advanced stage of malignancy.

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Section: Discussionmentioning

confidence: 87%

Progressive loss of endothelial P-selectin expression with increasing malignancy in colorectal cancer

Peeters

Ruers

Westphal

et al. 2005

Laboratory Investigation

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“…While cancerous tissues have for many years been known to be histamine rich, our studies indicates that histamine is derived largely from Hdc + CD11b + Ly6G + IMCs. In previous studies, H 2 R antagonists have generally not been shown to be effective in the treatment of cancer 43–45; this may have been due, in part, to their inhibitory effects on the differentiation of IMCs. However, further studies are needed to assess the impact on cancer risk of HR antagonists, particularly H 1 R antagonists that have not been examined46.…”

Section: Discussionmentioning

confidence: 97%

Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid cells

Yang

Asfaha

et al. 2010

Nat Med

186

220

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Histidine decarboxylase (HDC), the unique enzyme responsible for histamine generation, is highly expressed in myeloid cells but its function is poorly understood. Here, we show that Hdc knockout mice exhibit a markedly increased rate of colon and skin carcinogenesis. Using Hdc-EGFP BAC transgenic mice, we demonstrate 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 wildtype recipients results in increased CD11b+Ly6G+ cell mobilization and reproduces the cancer susceptibility phenotype. In addition, IMCs from Hdc knockout mice promote the growth of cancer xenografts and colon cancer cells downregulate Hdc expression through promoter hypermethylation and inhibits myeloid cell maturation. Exogenous histamine induces the differentiation of IMCs and suppresses their ability to support the growth of xenografts. These data indicate key roles for Hdc and histamine in myeloid cell differentiation, and CD11b+Ly6G+ IMCs in early cancer development.

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“…High histamine concentrations have been reported in a wide number of human and experimental tumors [37][38][39] and also histamine receptors are expressed in different malignant cell types in which they can be associated to multiple signaling pathways [9,14,15,25,[40][41][42]. In addition, different human tumors such as melanoma, colon and breast carcinomas showed higher histamine concentration compared with surrounding normal tissues [43][44][45][46]. In this study, we have demonstrated for the first time the presence of the fourth histamine receptor subtype in two human melanoma cell lines.…”

Section: Discussionmentioning

confidence: 99%

Role of H4 receptor in histamine-mediated responses in human melanoma

et al. 2011

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We have previously reported that histamine at micromolar concentrations reduces the proliferation of melanoma cell lines. It is also known that melanoma cells express histamine H 1 , H 2 , and H 3 receptors. The aim of this study was to investigate the presence of histamine H 4 receptor (H 4 R) in human melanoma cells and its associated biological processes. To better understand the importance of histamine in tumor development, we explored the expression of H 4 R in human melanoma tissue biopsies. The expression of H 4 R in WM35 and M1/15 cells was analyzed by reverse-transcription-PCR, western blot, and immunocytochemistry. To characterize the biological responses we evaluated cell proliferation by clonogenic assay and 5-bromo-2 0 -deoxyuridine incorporation. In addition, cell senescence and differentiation were determined by b-galactosidase enzyme assay and dopa oxidase activity, respectively. The expression levels of H 4 R were determined by immunohistochemistry in 19 samples of human malignant lesions. Results indicate that melanoma cells express H 4 R at the messenger RNA and protein levels. By using histamine agonists, antagonists, and H 4 R small-interfering RNA we showed that the inhibitory effect of histamine on proliferation was in part mediated through the stimulation of the H 4 R. The decrease in proliferation was associated with an induction of cell senescence and an increase in melanogenesis, which is a differentiation marker of these cells. Furthermore, H 4 R was expressed in 42% of human melanoma biopsies. To our knowledge, this is the first report that describes the presence of the H 4 R in melanoma cells and tissue, suggesting a potential therapeutic application of H 4 R ligands.

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Histamine content in colorectal cancer. Are there sufficient levels of histamine to affect lymphocyte function?

Cited by 27 publications

References 18 publications

Progressive loss of endothelial P-selectin expression with increasing malignancy in colorectal cancer

Progressive loss of endothelial P-selectin expression with increasing malignancy in colorectal cancer

Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid cells

Role of H4 receptor in histamine-mediated responses in human melanoma

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