Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metalloproteinases are thought to be important for tumor invasion and metastasis. We used in situ hybridization with 35S-labeled cRNA probes to localize sites of expression for 92-kDa type IV collagenase mRNA in sections of nodular basal cell carcinoma. Positive signal for 92-kDa type IV collagenase mRNA was detected in eosinophilic granulocytes within inflammatory infiltrates surrounding the tumor nodules. Eosinophils, however, were not adjacent to tumor cells, suggesting that metalloenzyme production by these granulocytes in this disease may be targeted more to stromal components than to remodeling or destruction of the basement lamina. The identity of the eosinophils was confirmed by cell morphology and specific histochemical staining. No resident or other migratory cells were positive for enzyme mRNA in these samples. Signal specificity for in situ hybridization was shown by a duplication of the results with complementary oligomeric probes and by a lack of signal in sections hybridized with a sense RNA probe or nonspecific oligomer. No signal for 92-kDa type IV collagenase mRNA was detected in circulating eosinophils or in eosinophils associated with Hodgkin's lymphoma. These data suggest that eosinophils migrate into the dermis and express type IV collagenase in response to basal cell carcinoma and that this process may have a role in tumor growth.
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PMID:Expression of 92-kDa type IV collagenase mRNA by eosinophils associated with basal cell carcinoma. 140 8

Secreted metalloproteinases (MPs) and their specific inhibitors (TIMPs, tissue inhibitors of MPs) are important mediators of extracellular matrix metabolism. Previous studies have linked either excessive MP release or reduced TIMP-1 production to the invasive and metastatic phenotypes of cancer cells. In the present study we investigated the relationship between the expression of TIMP-1 and the clinical behavior of 28 non-Hodgkin's lymphomas. Northern blot analysis showed that levels of TIMP-1 mRNAs correlated directly with clinical aggressiveness: tumors in the high-grade category contained the highest levels of TIMP-1 transcripts approaching those found in maximally growth factor-stimulated fibroblasts in vitro. In situ hybridization localized the TIMP-1 expression to stromal cells of endothelial and fibroblastic origin. In contrast, transcripts hybridizing with metalloproteinase gene probes (interstitial collagenase and 72-Kd type IV collagenase) were expressed at very low levels in malignant lymphomas and their expression was not coordinately regulated with that of TIMP-1. The majority of tumors expressed either interstitial collagenase or 72-Kd type IV collagenase, and only a small number expressed both. Interstitial collagenase transcripts were only detected in high-grade tumors. The relative levels of TIMP-1 expression did not correlate with the degree of fibrosis of the tumors. Our data suggest the importance of tumor-stromal interactions in non-Hodgkin's lymphomas, and moreover, our results indicate a possible relationship between high-level, localized expression of TIMP-1 and the malignant phenotype of high-grade advanced-stage lymphomas.
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PMID:Tissue inhibitor of metalloproteinases-1 (TIMP-1) RNA is expressed at elevated levels in malignant non-Hodgkin's lymphomas. 164 4

We have studied the expression of gelatinase A, gelatinase B, interstitial collagenase, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in reactive lymphoid cells, as well as in a series of cell lines derived from neoplasms of B- and T-cell lineage. Using both Northern blot analysis and zymography, gelatinase B activity was detected by zymography in two Burkitt cell lines and in a tonsillar cell suspension, while gelatinase A and interstitial collagenase activities were not detected by either method. TIMP-1 expression was demonstrated by Northern blot analysis in the multipotential neoplastic K-562 cell line, the high grade Burkitt's B-cell lymphoma lines, isolated tonsillar B cells and at low levels in peripheral blood T cells, but was not expressed in any of the neoplastic T-cell lines or isolated peripheral blood B cells. In contrast, TIMP-2 expression was restricted to tissues containing cells of T-cell lineage with high levels being observed in the neoplastic T-cell lines and lower levels in normal peripheral blood T cells and hyperplastic tonsil. Expression of TIMP-1 and TIMP-2 was confirmed at the protein level by reverse zymography and immunofluorescence assays using antihuman TIMP polyclonal antibodies. Expression of gelatinase B by the high grade B-cell Burkitt's lymphoma cell lines is consistent with previous findings in large cell immunoblastic lymphomas and indicates that this enzyme may play an important role in high grade non-Hodgkin's lymphomas. TIMP expression correlated with cell lineage in that TIMP-1 was primarily observed in B cells and TIMP-2 was restricted to T cells.
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PMID:Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in reactive and neoplastic lymphoid cells. 905 54