Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies were raised against seven major matrix metalloproteinases: stromelysin-1 (MMP-3), stromelysin-2 (MMP-10), stromelysin-3 (MMP-11), interstitial collagenase (MMP-1), M(r) 72,000 type IV collagenase (72 kDa type IV collagenase, MMP-2), M(r) 92,000 type IV collagenase (92 kDa type IV collagenase, MMP-9) and matrilysin (PUMP, MMP-7) as well as against prolyl 4-hydroxylase, to study the expression of these collagenolytic enzymes in normal liver in relation to the activity of collagen synthesis. Tissue samples of four normal human livers, three hepatocellular carcinomas and one cholangiocellular carcinoma were analysed. In normal liver we found expression of stromelysin-1, stromelysin-3, interstitial collagenase, M(r) 72,000 and M(r) 92,000 type IV collagenases and varying expression of prolyl 4-hydroxylase. Stromelysin-2 was inconsistently detectable; matrilysin was not found. In hepatocellular carcinoma the expression pattern of matrix metalloproteinases showed only minor changes compared with the normal tissue; stronger signals than in normal tissue were seen for stromelysin-1, and stromelysin-2 was also strongly positive. M(r) 72,000 and M(r) 92,000 type IV collagenases and interstitial collagenase were less strongly expressed; stromelysin-3 was unchanged. Expression of prolyl 4-hydroxylase was also increased compared with normal liver. Matrilysin was only seen in cholangiocellular carcinoma, which showed a completely different pattern of matrix metalloproteinase expression. Our results show that metalloproteinases are expressed in human liver with much greater abundance than previously described. Their expression pattern is not changed fundamentally in hepatocellular carcinoma but is completely different from that of other tumour tissues such as cholangiocellular carcinoma.
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PMID:Expression pattern of matrix metalloproteinases in human liver. 763 22

Stromelysin-3 expression was studied by Northern blotting in 222 tissue samples including primary and metastatic breast carcinoma and normal breast tissue. Uninvolved breast tissue from mastectomy specimens, normal breast tissue from reduction mammoplasties and normal lymph nodes did not contain stromelysin-3 mRNA. About 62% of primary and metastatic breast carcinomas, but only 1 of 10 in situ ductal carcinomas, expressed stromelysin-3. Stromelysin-3 mRNA was found more often in estrogen-receptor-positive carcinomas and in histological grade-1 carcinomas. There was no significant correlation between stromelysin-3 expression and other prognostic factors, including tumor size, lymph-node involvement, age of patient, vascular invasion and cathepsin-D.
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PMID:Stromelysin-3 expression in breast cancer biopsies: clinico-pathological correlations. 824 74

A new member of the matrix metalloproteinase (MMP) family of enzymes has been cloned from a human breast carcinoma cDNA library. The isolated cDNA contains an open reading frame 1554 bp long, encoding a polypeptide of 518 amino acids. The predicted amino acid sequence displays a similar domain organization as the remaining MMPs, including a prodomain with the activation locus, the zinc-binding site, and the hemopexin domain. In addition, it contains a C-terminal extension, rich in hydrophobic residues and similar in size to those present in the different membrane-type MMPs (MT-MMPs) identified to date. On the basis of these structural characteristics, this novel MMP has been tentatively called MT4-MMP, because it represents the fourth member of this subclass of MMPs characterized mainly by the occurrence of putative transmembrane domain in their amino acid sequences. MT4-MMP also contains a nine-residue insertion between the propeptide and the catalytic domain, which is a common feature of MT-MMPs and stromelysin-3. This amino acid sequence insertion ends with the consensus sequence R-X-R/K-R, which seems to be essential in the activation of these proteinases by furin. Northern blot analysis of polyadenylated RNAs isolated from a variety of human tissues revealed that the MT4-MMP gene (MMP-17) is expressed mainly in the brain, leukocytes, the colon, the ovary, and the testis. The expression of MT4-MMP in leukocytes together with its putative membrane localization suggest that this enzyme could be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators such as tumor necrosis factor-alpha. In addition, MT4-MMP transcripts were detected in all breast carcinomas, as well as in all breast cancer cell lines analyzed in the present work. On the basis of these expression data in breast tumors, a potential role for human MT4-MMP in the tumoral process is also suggested.
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PMID:Molecular cloning of a novel membrane-type matrix metalloproteinase from a human breast carcinoma. 864 Jul 82

Stromelysin-3 is produced in the stroma of various malignant tumors, and in breast carcinoma there seems to be a positive correlation between aggressive disease and intensity of stromelysin-3 expression, suggesting that stromelysin-3 participates in the tumor spread. In basal cell carcinoma, previous findings on stromelysin-3 have been inconclusive in this respect. Our study was undertaken to determine the pattern of stromelysin-3 production in relation to different histologic subtypes and stromal reactions in basal cell carcinoma. By in situ hybridization, stromelysin-3 mRNA was detected in stromal fibroblastic cells in 51/56 samples. Furthermore, there was a significant correlation between strong signal for stromelysin-3 mRNA and infiltrative tumor growth. In all tumors, there was ongoing collagen synthesis as shown by a signal for procollagen I mRNA; this signal co-localized with stromelysin-3 around tumor nests. Our findings suggest a link between stromelysin-3 and fibrotic stromal response, which prompted us to evaluate the expression of stromelysin-3 in other fibrotic skin tumors. Interestingly, stromelysin-3, co-localizing with procollagen I mRNA, was consistently expressed in lesional cells in dermatofibromas (19/19), but not in dermatofibrosarcomas (0/7). Thus, our results indicate that in addition to being a marker for malignant disease, stromelysin-3 is produced by fibroblastic cells associated with benign fibrosis. A subset of cells producing stromelysin-3 appears to be myofibroblasts as demonstrated by immunoreactivity for alpha smooth muscle actin in both basal cell carcinoma and dermatofibroma.
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PMID:Stromelysin-3 mRNA associated with myofibroblasts is overexpressed in aggressive basal cell carcinoma and in dermatofibroma but not in dermatofibrosarcoma. 875 54

Stromelysin-3 has been recently described in association with the stroma of different types of cancer including colorectal carcinomas. This article reports the detection of transcripts for stromelysin-3 (matrix metalloproteinase-11 [MMP-11]) in extracts of tissue from colorectal carcinomas using the technique of reverse transcription-polymerase chain reaction (RT-PCR). In 12 cases of primary colon carcinoma, stromelysin-3 messenger RNA (mRNA) was detected after 25 cycles, whereas this procedure did not reveal stromelysin-3 mRNA expression in one rectal carcinoma micrometastasis to the liver or in normal colon tissue (controls) after 30 cycles of PCR. However, stromelysin-3 mRNA was detected in normal colon specimens after 45 cycles. The high sensitivity of this technique allows application for the investigation of the expression of stromelysin-3 in small amounts of tissue.
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PMID:Amplification of stromelysin-3 transcripts from carcinomas of the colon. 881 93

Pseudoinvasion in colorectal adenomas is often difficult to distinguish from invasive carcinoma. Previous studies have indicated that expression of stromelysin-3 (ST-3), one of the metalloproteinase family of enzymes, may be useful for the identification of early invasive carcinoma. The goal of our study was to detect ST-3 expression in colorectal adenomatous polyps to see if it could be helpful for the differential diagnosis of pseudoinvasion vs. true invasion. We studied 25 polypectomy specimens which were divided histologically into 2 groups; the first consisted of 15 adenomas with invasive carcinoma, 8 of these carcinomas were more diffusely infiltrative (pT1), and 7 tended to be expansively invasive. The second group was composed of 10 adenomas with pseudoinvasion. A 35S labelled cDNA probe was used for in situ hybridization (ISH) and a monoclonal antibody (5ST-4A9) for immunohistochemistry (IHC). The distribution of ST-3 expression as detected by IHC and ISH was identical. All diffusely infiltrative carcinoma cases showed ST-3 expression, but only focally in 2 cases with marked lymphocytic infiltration. None of the expansive carcinoma or pseudoinvasion cases showed ST-3 expression. ST-3 expression seems to be an indicator of invasion, but a negative reaction for ST-3 does not rule out an expansive invasive neoplasm or a diffusely infiltrative invasive tumour with a dense lymphocytic reaction.
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PMID:Stromelysin-3 expression in early (pT1) carcinomas and pseudoinvasive lesions of the colorectum. 909 78

Matrix metalloproteinases (MPs) constitute a family of proteolytic enzymes (proteases) that degrade extracellular matrix (ECM) and promote the local or metastatic potential of carcinoma cells, and whose action is restrained by special inhibitors (metalloproteinase inhibitors; MIs). We assessed the role of the MPs stromelysin-3 (STR-3), putative metalloproteinase-1 (PUMP-I), and the gelatinases of molecular weights 72 kDa and 92 kDa, as well as the role of their inhibitors tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, as markers of metastatic potential in 25 fresh biopsies of squamous-cell lung carcinomas (SCLCs). We examined levels of messenger ribonucleic acid (mRNA) expression for these MPs and inhibitors through Northern blot analysis in 10 carcinomas of high-to-moderate differentiation without lymph-node involvement, and in 15 infiltrative carcinomas of moderate-to-low differentiation with lymph-node involvement. Five cases with significant epithelial atypia and five samples with normal mucosa were used as controls. Expression of STR-3 and TIMP-2 was also assessed immunohistochemically with the avidin-biotin-complex (ABC) technique. We noticed a progressive increase in the expression levels of MPs, especially of STR-3, and of TIMP-2, from the stage of epithelial atypia to the detection of carcinoma, finding the highest values of these substances among carcinomas of low differentiation with nodal metastases. These findings were also confirmed with immunohistochemical analysis. Our results suggest that there is a significant association of the expression of MPs and MIs with both the local and metastatic potential and the degree of cellular differentiation of SCLC, and that this association is clinically important because of its prognostic and therapeutic implications.
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PMID:Association of expression of metalloproteinases and their inhibitors with the metastatic potential of squamous-cell lung carcinomas. A molecular and immunohistochemical study. 941 77

Matrix metalloproteases represent a family of proteases secreted as latent inactive enzymes able to degrade the majority of extracellular matrix components. These enzymes are overexpressed during several pathological tissue remodelings including tumor progression and tumor invasion. It was indeed classically admitted that matrix metalloproteases involved in tumoral progression were preferentially expressed by cancerous cells. Our studies on gelatinase A and stromelysin-3 have, however, demonstrated that their messenger RNAS are detected in fibroblasts of the peritumoral stroma in human mammary carcinoma and not in the cancerous cells themselves. By immunohistochemistry, we have detected gelatinase A in the cytoplasm of fibroblasts and at the surface of the tumor cells. This membrane localization of the protein could result from its binding, following secretion by the neighbouring stromal cells, to a specific binding site expressed at the surface of the carcinoma cells. These cells are indeed able to induce an increased proteolytic activity by enhancing the transcription of these enzymes by peritumoral fibroblasts. These enzymes represent therefore potential targets for the development of new therapeutic strategies.
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PMID:[Stromal proteases in the progression of breast cancer]. 953 65

Histopathological differentiation between desmoplastic trichoepithelioma (DTE) and morphealike basal cell carcinoma (BCC) is a difficult problem because of their similar morphological features. The matrix metalloproteinase stromelysin-3 (ST-3), which is expressed as a specific fibroblastic factor especially surrounding carcinoma cells, was studied in these both conditions of wholly different clinical outcome. Using formalin-fixed paraffin-embedded tissues, we found positive immunoreactivity for ST-3 in fibroblastic cells surrounding morphealike BCC cells in 34 (68%) of 50 cases, whereas the epithelial tumor cells themselves were negative. In none of the 12 cases of DTE did we observe expression of ST-3 in fibroblasts. We conclude that the antibody against ST-3 protein is an immunohistochemical marker to distinguish morphealike BCC from DTE.
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PMID:Stromelysin-3: a potent marker for histopathologic differentiation between desmoplastic trichoepithelioma and morphealike basal cell carcinoma. 955 81

The purpose of this study was to investigate the association among matrix metalloproteinases (gelatinases A and B, stromelysin-3 (ST3) and matrilysin) mRNAs expressed in primary breast carcinomas and standard prognostic parameters and clinical outcome. mRNA levels were determined by Northern analysis in samples of 81 breast cancer patients (median follow-up, 40 months) and 27 samples of uninvolved adjacent breast tissue. Proteases were expressed by the majority of the tumors and normal breast tissues examined. ST3, gelatinase A and matrilysin mRNAs were more often expressed at high levels in carcinomatous than in normal breast tissues. Differences in the distribution of gelatinase B mRNA were not found. However, paired normal tissues generally produced weaker signals when compared to matched tumor samples. Univariate analysis showed no significant association of gelatinase A and matrilysin mRNAs with the classical prognostic markers (age, menopausal status, stage, size, nodal status, vascular infiltrate, necrosis, steroid receptors, metastasis and survival). Overexpression of ST3 was more frequently found in tumors of post-menopausal women (P < 0.022). Elevated expression of gel B mRNA was associated with the presence of vascular infiltrate (P < 0.026), necrosis (P < 0.039), PR negative tumors (P < 0.014) and inversely correlated to the number of survivors (P < 0.021). Multivariate analysis including 68 patients for whom all information was available indicated that neither stromelysin correlated significantly with pathological, clinical or biochemical features. High levels of gelatinase A and B mRNAs were inversely associated with the number of survivors. Our findings suggest that measurements of gelatinase A and B mRNAs expression in breast carcinoma may help to identify patients with an aggressive form of the disease.
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PMID:Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast carcinomas: clinico-pathological correlations. 993 4


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