Mast-cell secretion and angiogenesis, a quantitative study in rats and mice

Norrby, Klas; Jakobsson, Anders; Sörbo, Jan

doi:10.1007/bf02899089

Cited by 51 publications

(26 citation statements)

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“…Tumors injected into mast-cell deficient mice [17] or into mice treated with inhibitors of mast cell degranulation [18,19] show decreased tumor vascularity, tumor growth, and metastasis, indicating that mast cell granule products enhance tumor growth and metastasis, leading to the suggestion that anti-mast cell agents may be useful in cancer chemotherapy. Endothelial cell migration and proliferation will accelerate tumor angiogenesis around gastric cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis

et al. 1999

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Abstract:Background. Increased numbers of mast cells are found in various solid tumors. To investigate the role of mast cells in the vicinity of gastric cancer cells, we used special staining and an immunohistochemical technique. Methods. Specimens were surgically obtained from 102 patients with gastric cancer. Mast cells around the tumor edge of gastric cancer nests were counted by staining with 0.05% toluidine blue solution. Blood vessels in these areas were also counted, by immunohistochemical staining of endothelial cells for factor VIII. Results. The average number of mast cells and blood vessels in gastric cancer specimens was significantly higher than that in normal gastric tissue. Specimens from patients with advanced disease with metastases to lymph nodes had more mast cells than specimens from patients with early-stage disease. Mast cells in specimens from patients with metastatic lymph nodes were significantly increased in comparison with numbers in specimens from those without nodal metastases. Mast cell numbers in the specimens of patients with lymphatic or blood vessel invasion were significantly higher than numbers in specimens from patients without such invasion. Mast cells were localized near the new vessels around gastric cancer cells. Mast cell numbers increased as the number of blood vessels increased (correlation coefficient, 0.783). Postoperative survival curves revealed that patients with increased numbers of mast cells had a poor prognosis. Conclusions. All these results suggest that mast cell accumulation at the tumor site may lead to increased rates of tumor vascularization and, consequently, increased rates of tumor growth and metastasis.

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Section: Discussionmentioning

confidence: 99%

Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis

et al. 1999

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“…An agent that selectively activates the mesenteric mast cells in rats have been used, by which mastcell-mediated angiogenesis was demonstrated for the first time [6,54,79]. Inflammatory cytokines such as IL-1-α [80], IL-8 [81], TNF-α [82], or a growth factor such as bFGF [56] or VEGF [58] have also been tested.…”

Section: Assay Set-upmentioning

confidence: 99%

In vivo models of angiogenesis

2006

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“…Mast cells have been implicated in the generation of an angiogenic response in various in vitro and in vivo studies (Kessler et al, 1976;Azizkhan et al, 1980;Wilson, 1985;Clinton et al, 1988;Starkey et al, 1988;Norrby et al, 1989;Meininger et al, 1995). The intimate anatomic association between mast cells and the vasculature and the increased rate of appearance of the cells during tumor growth, wound healing, and inflammation, processes that are all accompanied by neovascularization, support this assumption (Meininger and Zetter, 1992).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Storage, and Release of Vascular Endothelial Growth Factor/Vascular Permeability Factor (VEGF/VPF) by Human Mast Cells: Implications for the Biological Significance of VEGF₂₀₆

Grützkau

Krüger‐Krasagakes

Baumeister

et al. 1998

MBoC

311

219

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Mast cells have been implicated in various diseases that are accompanied by neovascularization. The exact mechanisms by which mast cells might mediate an angiogenic response, however, are unclear and therefore, we have investigated the possible expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in the human mast cell line HMC-1 and in human skin mast cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that mast cells constitutively express VEGF121, VEGF165, and VEGF189. After a prolonged stimulation of cells for 24 h with phorbol 12-myristate 13-acetate (PMA) and the ionophore A23187, an additional transcript representing VEGF206 was detectable, as could be verified by sequence analysis. These results were confirmed at the protein level by Western blot analysis. When the amounts of VEGF released under unstimulated and stimulated conditions were compared, a significant increase was detectable after stimulation of cells. Human microvascular endothelial cells (HMVEC) responded to the supernatant of unstimulated HMC-1 cells with a dose-dependent mitogenic effect, neutralizable up to 90% in the presence of a VEGF-specific monoclonal antibody. Flow cytometry and postembedding immunoelectron microscopy were used to detect VEGF in its cell-associated form. VEGF was exclusively detectable in the secretory granules of isolated human skin mast cells. These results show that both normal and leukemic human mast cells constitutively express bioactive VEGF. Furthermore, this study contributes to the understanding of the physiological role of the strongly heparin-binding VEGF isoforms, since these were found for the first time to be expressed in an activation-dependent manner in HMC-1 cells.

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Mast-cell secretion and angiogenesis, a quantitative study in rats and mice

Cited by 51 publications

References 25 publications

Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis

Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis

In vivo models of angiogenesis

Synthesis, Storage, and Release of Vascular Endothelial Growth Factor/Vascular Permeability Factor (VEGF/VPF) by Human Mast Cells: Implications for the Biological Significance of VEGF₂₀₆

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Mast-cell secretion and angiogenesis, a quantitative study in rats and mice

Cited by 51 publications

References 25 publications

Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis

Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis

In vivo models of angiogenesis

Synthesis, Storage, and Release of Vascular Endothelial Growth Factor/Vascular Permeability Factor (VEGF/VPF) by Human Mast Cells: Implications for the Biological Significance of VEGF206

Contact Info

Product

Resources

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Synthesis, Storage, and Release of Vascular Endothelial Growth Factor/Vascular Permeability Factor (VEGF/VPF) by Human Mast Cells: Implications for the Biological Significance of VEGF₂₀₆