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)

Autocrine interleukin 3 (IL-3)-secreting tumors were generated from an IL-3-dependent mouse mast cell line (PB-3c) after introduction of the v-H-ras oncogene. Tumor progression was characterized by four distinct phenotypes. The first corresponded to immortalized mast cells unresponsive to the oncogenic effect of v-H-ras. The second was expressed in a clonable subpopulation of PB-3c cells and was marked by the competence to form v-H-ras-dependent tumors (immortalized transformation competence). The third was a direct effect of v-H-ras expression on all PB-3c cells and was characterized in vitro by a reduced IL-3 requirement. Upon injection of v-H-ras-expressing, transformation-competent cells into mice, the final, fully malignant phenotype developed with a long latency period and was marked in vitro by independence of exogenous IL-3 and by autocrine IL-3 stimulation. Northern (RNA) blot analysis and an RNase A-T1 protection assay showed that IL-3 production was strictly associated with the tumor phenotype. Two of six tumors showed an alteration at the 5' region of the IL-3 gene. We conclude that v-H-ras required complementation by IL-3 gene rearrangement or an alternate event to generate autocrine mastocytomas.
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PMID:A v-H-ras-dependent hemopoietic tumor model involving progression from a clonal stage of transformation competence to autocrine interleukin 3 production. 249 44

Mast cell participation in immune responses, tumor progression, and vascularization has been studied extensively in vitro. In situ investigation of mast cells in routinely processed tissues is hampered by difficulty in reliable detection of mast cells. We studied the tissue density of mast cells using a morphometric point-counting technique in 1 microm-thick, Giemsa-stained, tissue sections from epon-embedded samples of skin biopsies. This technique has been demonstrated to be an accurate and reproducible method for determining mast cell density. Mast cell density in 15 cases of invasive melanoma was compared to that of 9 cases of benign melanocytic nevi and 4 cases of melanoma in situ. Mast cell density was greatest in invasive melanoma (mean density = 0.61 vol.%). The mean density of mast cells in nevi and in situ melanoma was 0.33 and 0.5 respectively. Six of 15 cases of melanoma had mast cell densities > 0.6, whereas mast cell density did not exceed 0.6 in any cases of melanoma in situ or benign melanocytic nevi (p < 0.02). Our findings confirm an increase in mast cell tissue density in some cases of invasive melanoma when compared to mast cell density in benign nevi and in situ melanoma.
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PMID:Increased mast cell density in invasive melanoma. 950 38

The aim of the present study was the ultrastructural characteristics of mast cell (MC) involved in host antitumor responses induced by local (i.t.) administration of recombinant human tumor necrosis factor alpha (rhTNF-alpha) in the primary focus of methA fibrosarcoma. MC were involved in tumor interstitium remodeling. Numerous mitochondria, well-developed RER and Golgi apparatus, clusters of polyribosomes, considerable polymorphism of granules and differentiated lamellar structures which frequently presented myelinic forms were observed after rhTNF-alpha application. In the study numerous fibres of the fibrous tissue, richly vascularized, occurred in the peripheral and intermediate tumor zones. Cluster of MC and tumor cells were seen on the border of the necrotic foci. However, proteolytic enzymes released by MC cause interstitial lysis, ensuring the place for tumor growth, and are involved in angiogenesis. Thus, it is not clear whether MC contribute to the inhibition of tumor growth or have an adjunctive role in tumor progression.
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PMID:Effect of the cytokine rhTNF-alpha on the population of mast cells in the growth of MethA fibrosarcoma--a TEM study. 1182 Jun 6

The occurrence of pathologically stable mRNAs of proto-oncogenes, growth factors and cyclins has been proposed to contribute to experimental and human oncogenesis. In normal resting cells, mRNAs containing an AU-rich element (ARE) in their 3' untranslated region are subjected to rapid degradation. Tristetraprolin (TTP) is an RNA-binding zinc-finger protein that promotes decay of ARE-containing mRNAs. Here we report that TTP acts as a potent tumor suppressor in a v-H-ras-dependent mast cell tumor model, where tumors express abnormally stable interleukin-3 (IL-3) mRNA as part of an oncogenic autocrine loop. Premalignant v-H-ras cells were transfected with TTP and injected into syngeneic mice. TTP expression delayed tumor progression by 4 weeks, and late appearing tumors escaped suppression by loss of TTP. When transfected into a fully established tumor line, TTP reduced cloning efficiency in vitro and growth of the inoculated cells in vivo. Transgenic TTP interfered with the autocrine loop by enhancing the degradation of IL-3 mRNA with concomitant reduction of IL-3 secretion. Our data establish the ARE as an antioncogenic target in a model situation, underline the importance of mRNA stabilization in oncogenesis and show for the first time that tumor suppression can be achieved by interfering with mRNA turnover.
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PMID:A novel mechanism of tumor suppression by destabilizing AU-rich growth factor mRNA. 1278 64

HL is a malignant lymphoma characterized by a small number of malignant HRS cells among a major population of infiltrating reactive cells, e.g., lymphocytes and eosinophils. We previously reported that mast cells are present in HL-affected lymph nodes and therein are the predominant CD30L-expressing cells. The CD30L expressed on mast cells is functionally active and can provide stimulatory signals to HRS cells. Thus, mast cells constitute an important portion of the infiltrating reactive cells that contribute to tumor progression in HL. Control of the recruitment of this previously unrecognized cell and its interactions with tumor cells are essentially unknown. To elucidate if mast cells might be specifically attracted to the tumor area by chemokines produced by HRS cells, we investigated chemokine expression in HL cell lines and in vivo. By RNase protection assay, mRNA expression of several chemokines could be detected in the cell lines. Despite the heterogeneous expression profile exhibited by the cell lines, 4 of 5 expressed CCL5 (RANTES) mRNA. RT-PCR and immunohistochemistry confirmed expression of CCL5 in vivo. Furthermore, secreted CCL5 was detected in conditioned media from 3 of the cell lines. In a migration assay, we found that CCL5 present in conditioned medium could induce mast cell migration. Taken together, our results suggest that CCL5 produced by HRS cells is one mechanism by which mast cells can be attracted into the tumor tissue in HL.
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PMID:Expression of CCL5/RANTES by Hodgkin and Reed-Sternberg cells and its possible role in the recruitment of mast cells into lymphomatous tissue. 1294 94

The objective of this study was to evaluate by immunohistochemical means the nuclear expression of p27 and p21 proteins in cutaneous mast cell tumors and histiocytomas of dogs. In mast cell tumors, nine of the 13 grade I tumors, 13 of the 19 grade II tumors, and 10 of the 15 grade III tumors showed no detectable or mild p27 immunoreactivity. In contrast, one of the 13 grade I tumors, 12 of the 19 grade II tumors, and 11 of the 15 grade III tumors showed moderate or marked p21 immunoreactivity. Nineteen of the 28 histiocytomas showed no detectable or mild p27 immunoreactivity, and 24 cases showed moderate or marked p21 immunoreactivity. These findings indicate that a loss or absence of p27 expression is an early pathogenic event in mast cell and histiocyte tumorigenesis and that p21 expression may be a marker of mast cell tumor progression and histiocytoma cell proliferation.
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PMID:Immunohistochemical expression of p27 and p21 in canine cutaneous mast cell tumors and histiocytomas. 1513 84

Mast cells have been observed in numerous types of tumors; however, their role in carcinogenesis remains poorly understood. The majority of epidemiological evidence suggests a negative association between the presence of mast cells and tumor progression in breast, lung and colonic neoplasms. Intestinal adenomas in the multiple intestinal neoplasia (Min, APC(Min/+)) mouse displayed increased numbers of mast cells and increased abundance of mast cell-associated proteinases as determined by transcriptional profiling with the Hu/Mu ProtIn microarray. To examine the role of mast cells in intestinal tumorigenesis, a mutant mouse line deficient in mast cells, Sash mice (c-kit(W-sh/W-sh)), was crossed with the Min mouse, a genetic model of intestinal neoplasia. The resulting mast cell-deficient Min-Sash mice developed 50% more adenomas than littermate controls and the tumors were 33% larger in Min-Sash mice. Mast cell deficiency did not affect tumor cell proliferation; however, apoptosis was significantly inhibited in mast cell-deficient mice. Mast cells have been shown to act as critical upstream regulators of numerous inflammatory cells. Neutrophil, macrophage and T cell populations were similar between Min and Min-Sash mice; however, eosinophils were significantly less abundant in tumors obtained from Min-Sash animals. These results indicate a protective, antitumor role of mast cells in a genetic model of early-stage intestinal tumorigenesis.
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PMID:A protective role of mast cells in intestinal tumorigenesis. 1825 1

Canine cutaneous mast cell tumor (MCT) is very common disease in dogs, this is more aggressive than in other species. The biologic behavior of MCT is highly variable and a more accurate prognosis for these tumors needs to performed. The proto-oncogene c-kit is known to play a critical role in development and function of mast cells (MC). The aim of this study was to evaluate the expression of immunohistochemical pattern of c-kit in MCTs and to correlate these results with MC density (MCD) and intratumoral microvessel density (MVD). Our results confirm that a more aggressive biologic behavior of canine MCT is associated with the increased c-kit expression, further suggesting a new role for c-kit, as a useful marker, in diagnostic pathology and in tumor progression.
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PMID:Expression of proto-oncogene C-kit and correlation with morphological evaluations in canine cutaneous mast cell tumors. 1860 29

Various studies have shown the role of mast cells in chronic inflammatory states and in tumor growth. The study is designed to have an idea of the relationship of mast cell density (MCD) to gastric ulcer and cancer, to verify whether mast cell accumulation occurred in the two conditions especially in Indian patients and thus postulate that therapeutic strategies against mast cell mediators could be useful in treatment. Also, we want to review literature and attempt to explain our findings. A total of 240 patients, who underwent their first endoscopy and biopsy for a span of 21/2 years were studied retrospectively. Out of these, 210 cases that were either gastric ulcers or cancer were chosen for this MCD study. Biopsies were sectioned and stained routinely. Toluidine blue stain and copper grid was used to calculate MCD. Student's t-Test was used to calculate the statistical significance of MCD. MCD in benign ulcers was much higher than in control subjects. MCD in well-differentiated cancers showed MCD higher than control. Poorly-differentiated adenocarcinoma showed lower MCD than well-differentiated adenocarcinoma. It was concluded that the accumulation of mast cells in gastric ulcers is an inflammatory response. MCD is increased in well-differentiated gastric cancers, which may be a mast cell mediated immune response or mast cells may have a role in tumor angiogenesis and produce factors for tumor progression. Poorly-differentiated adenocarcinoma apparently lacks mast cell mediated anti-tumor response in some unexplained way.
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PMID:Evaluation of endoscopic biopsy in gastric lesions with a special reference to the significance of mast cell density. 1913 73

Platinum compounds are among the most used DNA-damaging anticancer drugs, however they can also be tailored to target biological substrates different from DNA, for instance enzymes involved in cancer progression. We recently reported that some platinum complexes with three labile ligands inhibit matrix metalloproteinase activity in a selective way. We have now extended the investigation to a series of platinum complexes having three chlorido or one chlorido and a dimethylmalonato leaving ligands. All compounds are strong inhibitors of MMP-3 by a noncompetitive mechanism, while platinum drugs in clinical use are not. Structural investigations reveal that the platinum substrate only loses two labile ligands, which are replaced by an imidazole nitrogen of His224 and a hydroxyl group, while it retains one chlorido ligand. A chlorido and a hydroxyl group are also present in the zinc complex inhibitor of carboxypeptidase A, whose active site has strong analogies with that of MMP-3.
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PMID:Mechanistic insight into the inhibition of matrix metalloproteinases by platinum substrates. 1975 21


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