Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF) has been implicated in the pathologic angiogenesis observed in psoriasis and other chronic inflammatory skin diseases that are characterized by enhanced expression of VEGF by epidermal keratinocytes and of VEGF receptors by tortuous microvessels in the upper dermis. To investigate the functional importance of chronic VEGF overexpression in vivo, we used a keratin 14 promoter expression cassette containing the gene for murine VEGF164 to selectively target VEGF expression to basal epidermal keratinocytes in transgenic mice. These mice demonstrated an increased density of tortuous cutaneous blood capillaries with elevated expression levels of the high affinity VEGF receptors, VEGFR-1 and VEGFR-2, most prominently during the neonatal period. In contrast, no abnormalities of lymphatic vessels were detected. In addition, the number of mast cells in the upper dermis was significantly increased in transgenic skin. Intravital fluorescence microscopy revealed highly increased leukocyte rolling and adhesion in postcapillary skin venules that were both inhibited after injection of blocking antibodies against E- and P-selectin. Combined blocking antibodies against intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 were without effect, whereas an anti-vascular cell adhesion molecule-1/VLA-4 antibody combination almost completely normalized the enhanced leukocyte adhesion in transgenic mice. This study reveals VEGF as a growth factor specific for blood vessels, but not lymphatic vessels, and demonstrates that chronic orthotopic overexpression of VEGF in the epidermis is sufficient to induce cardinal features of chronic skin inflammation, providing a molecular link between angiogenesis, mast cell accumulation, and leukocyte recruitment to sites of inflammation.
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PMID:Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. 966 79

The Copenhagen (COP) rat is extremely resistant to mammary cancer induction by carcinogens. Multiple genetic loci have been linked to the resistant phenotype, but the mechanisms underlying the resistance still remain unknown. Evidence has shown that the acquisition of angiogenic capacity is critical for tumor development. We, therefore, decided to investigate whether administration of angiogenic factor would enhance mammary carcinogenesis in the COP rat. Vascular endothelial growth factor (VEGF) was administered in a sustained releasing formula to pubescent female COP rats 2 weeks after N-nitroso-N-methylurea (NMU) treatment. Six months after NMU exposure, we found no difference in mammary tumor incidence between VEGF treated animals and controls. Analysis of VEGF expression, however, revealed different expression patterns in mammary epithelial cells of various origins. Mammary epithelial cells from pubescent susceptible Buffalo (BUF) and COP rats expressed substantial levels of VEGF messages, whereas cells prepared from 230-day-old rats showed negligible levels of VEGF mRNA. We also demonstrated that mammary epithelial cells from tumors developed in susceptible BUF rats expressed VEGF, whereas VEGF messages were barely detectable in tumors induced in COP rats. Furthermore, enlargement of the intramammary lymph nodes with prominent mast cells was observed in NMU treated COP rats, but not in NMU treated BUF rats. These results suggest that down regulation of VEGF expression is insufficient for resistance to mammary carcinogenesis, and that enhanced immune response, as evidenced by intramammary lymph node enlargement with mast cell accumulation, may also play a role in conferring resistance in the COP rat.
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PMID:Resistance to mammary carcinogenesis in Copenhagen rats: potential roles of vascular endothelial growth factor and mast cells. 1221 86

This paper reviews the role of mast cells in the development and progression of basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Mast cells accumulate around cutaneous malignancies. Current evidence suggests that mast cells contribute to the tumorigenesis of cutaneous malignancies through four mechanisms. (1) Immunosuppression: Ultraviolet-B radiation, the most important initiator of cutaneous malignancies, activates mast cells. Upon irradiation of the skin, trans-urocanic acid in the epidermis isomerizes to cis-urocanic acid, which stimulates neuropeptide release from neural c-fibers. These neuropeptides in turn trigger histamine secretion from mast cells, leading to suppression of the cellular immune system. (2) Angiogenesis: Mast cells are the major source of vascular endothelial growth factor in basal cell carcinoma and malignant melanoma. Vascular endothelial growth factor is one of the most potent angiogenic factors, which also induces leakage of other angiogenic factors across the endothelial cell wall into the matrix. Mast cell proteases reorganize the stroma to facilitate endothelial cell migration. As well, heparin, the dominant mast cell proteoglycan, assists in blood-borne metastasis. (3) Degradation of extracellular matrix: Through its own proteases, and indirectly via interaction with other cells, mast cells participate in degradation of the matrix, which is required for tumor spread. (4) Mitogenesis: Mast cell mediators including fibroblast growth factor-2 and interleukin-8 are mitogenic to melanoma cells. Current evidence supports an accessory role for mast cells in the development and progression of cutaneous malignancies. Emerging data, however, also suggest that mast cells might, in fact, have opposing roles in tumor biology, and the microenvironment could polarize mast cells to possess either promoting or inhibitory effects on tumors.
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PMID:Mast cells and cutaneous malignancies. 1625 17

Vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE-2) appear to play a critical role in tumour neovascularization. In this study, we have investigated the expression of VEGF and PGE-2 in 53 canine cutaneous mast cell tumours (MCTs). Immunohistochemistry of tissue sections revealed that VEGF and PGE-2 were expressed in all mast cell tumours studied. When the expression patterns of VEGF and PGE-2 were compared with tumour grade according to Patnaik criteria, the only significant correlation observed was between PGE-2 staining intensity and tumour pathological grade, with grade II and III tumours having higher PGE-2 staining, both in intensity and percentage of cells stained, than grade I tumours (P < 0.05).
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PMID:Immunohistochemical evaluation of prostaglandin E2 and vascular endothelial growth factor in canine cutaneous mast cell tumours. 2023 May 78