Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant glioma is a local invasive tumor in the central nervous system. The mRNA expression of five matrix metalloproteinases (MMPs) and two tissue inhibitors of metalloproteinases (TIMPs) was examined in surgical specimens of three brain tissues, two astrocytomas, four anaplastic astrocytomas and eleven glioblastomas, including recurrent one anaplastic astrocytoma and two glioblastomas. In the control brain tissues, mRNA expression was high for TIMP-2, low for gelatinase A and TIMP-1, and undetectable for gelatinase B, interstitial collagenase, stromelysin and matrilysin. Gelatinase B and TIMP-1 were concomitantly overexpressed in primary glioblastomas. In addition, the average expression level of gelatinase A increased 3.0 fold in astrocytomas and anaplastic astrocytomas and 6.0 fold in glioblastomas, compared to the brain tissues. Matrilysin was induced variably in more than half of the primary glioblastomas, and interstitial collagenase was slightly induced in some primary and recurrent glioblastomas. Stromelysin was characteristically not expressed in any gliomas, and the expression level of TIMP-2 did not significantly change in the gliomas. These results suggest that the concomitant increased expression of gelatinase A, gelatinase B and occasional matrilysin genes is associated with the malignancy of gliomas and accompanied by the increased expression of TIMP-1 gene.
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PMID:[Increased expression of gelatinases A and B, matrilysin and TIMP-1 genes in human malignant gliomas ]. 763 25

In this study, we investigated the correlation between the expression of MMP-2 and lymph node metastasis by analyzing 58 cases of primary lung cancer. Furthermore we studied expression of membrane-type MMP (MT-MMP) which was identified as an activator of MMP-2 and its relation to the activation ratio of MMP-2 in tumor tissues. Activated form of MMP-2 was detected specifically in the tumor tissues by zymography, and the activation ratio was significantly higher in 20 cases of the lymph node metastasis positive group than in other 38 cases. Additionally, northern blott analysis showed that MT-MMP was overexpressed in cancer tissues and that the expression of MT-MMP was closely related to the amount of activated form of MMP-2. These results indicated that MMP-2, which is activated by MT-MMP expressed on the surface of tumor cells, play a role in tumor metastasis by degrading surrounding basement membranes.
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PMID:[Expression of membrane-type matrix metalloproteinase (MT-MMP) and activation of MMP-2 in lung cancer]. 763 26

Matrilysin is a member of the matrix metalloproteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We examined the effects of over- and under-expression of matrilysin on the ability of colon cancer cells to migrate across an artificial membrane in vitro. Introduction of matrilysin caused colon cancer cells to become more invasive as assessed by an in vitro invasion assay. In contrast, expression of matrilysin was down-regulated by all trans-retinoic acid or by introduction of anti-sense matrilysin in BM314 colon cancer cells. This down-regulation caused these cells to become less invasive. We demonstrated a correlation between matrilysin level and the invasive potential of human colon cancer cells, implying an important role for matrilysin in the control of tumor invasion in vitro.
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PMID:Suppression of matrilysin inhibits colon cancer cell invasion in vitro. 770 51

From breast cancer cDNA libraries, we have cloned cDNAs that proved to correspond to the membrane-type matrix metalloproteinase (MT-MMP) recently identified in human placenta and proposed to be an activator of progelatinase A [Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E. & Seiki, M. (1994) Nature (London) 370, 61-65]. Using one of these cDNAs as a probe, we have detected MT-MMP gene expression in all 83 human carcinoma specimens examined by RNA in situ hybridization and have found MT-MMP transcripts in fibroblastic cells of tumor stroma but not in cancer cells. Comparison with other MMP genes expressed in fibroblastic cells of human carcinomas indicated that the expression pattern of the MT-MMP gene was more closely related to that of the gelatinase A gene than to those of the stromelysin 3 or interstitial collagenase genes. These observations are consistent with the hypothesis that MT-MMP and gelatinase A are cooperating during tumor progression and strengthen the concept that proteolytic activities originating from the stromal component of human carcinomas have a critical role in tumor progression.
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PMID:Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. 770 15

We identified a new matrix metalloproteinase (membrane type matrix metalloproteinase (MT-MMP)) that has a potential transmembrane (TM) domain at the C terminus and reported its expression on the surface of invasive tumor cells. The expression of MT-MMP induced specific activation of 72-kDa pro-gelatinase A (Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E., and Seiki, M. (1994) Nature 370, 61-65). Thus, MT-MMP on the cell surface is thought to play an important role in various physiological and pathological processes accompanying tissue remodeling. In this study, we demonstrated that the potential TM domain deduced from the amino acid sequence functions as a membrane linker when it is fused to a secretory protein, tissue inhibitor of matrix metalloproteinases-1. The pro-gelatinase A activation function of MT-MMP was abolished by truncation of the TM domain and recovered by fusing the MT-MMP mutant with the TM domain of interleukin 2 receptor alpha-chain. The truncated MT-MMP was released from the cells into the medium and detected as processed or modified forms. In spite of the deletion of the TM domain some portions of the mutant MT-MMP were still retained on the surface of cells. Thus, MT-MMP has an additional device to keep it on the cell surface. The TM domain however, plays an essential role in the pro-gelatinase A activation function of MT-MMP, probably regulating its fine orientation or the localization that is necessary to interact with substrate.
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PMID:The C-terminal region of membrane type matrix metalloproteinase is a functional transmembrane domain required for pro-gelatinase A activation. 782 14

Interest in orthotopic models has been generated by recent reports of increased invasive and metastatic potential demonstrated by tumor cell lines following injection into their tissue of origin rather than subcutaneously. We have previously demonstrated that transfection of the tumorigenic human prostate cell line, Du-145, with the metalloproteinase matrilysin increased its ability to invade the diaphragm following an intraperitoneal injection. In this study we compare the invasive and metastatic behavior of transfected Du-145 cell lines injected into the dorsal lateral lobe of the prostate to that observed when they are injected intraperitoneally. Immunohistochemistry was used to examine 37 orthotopically injected severe combined immunodeficient mice for local invasion and metastatic lesions. In addition, the effect of injection site on the level of expression of four genes thought to influence the invasiveness of tumor cells (matrilysin, stromelysin, TIMP-1, and TIMP-2), was determined by northern analysis of orthotopic and subcutaneous tumor tissue. The results demonstrate that the level of mRNA expression of the genes examined was similar at the two sites of injection and that the invasive properties of Du-145 cells following orthotopic implantation were comparable to that observed on the diaphragm following intraperitoneal injection. The advantages of the diaphragm invasion model are: less procedure-related mortality, ease of cell delivery, and provision of an easily orientated structure in which the earliest penetration of a basal lamina can be observed.
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PMID:Prostate tumor cell invasion: a comparison of orthotopic and ectopic models. 786 Feb 25

Matrix-degrading metalloproteinases play a major role in tissue remodeling. Recent studies have shown that enzymes of this class are constitutively expressed primarily by stromal cells and not by epithelium. Here we present immunohistochemical evidence that matrilysin is localized within epidermal cells in developing skin and in tumor cells of cutaneous malignancies. The expression of matrilysin protein in developing fetal skin (6-15 weeks) is localized primarily to the germinative basal cell layer of fetal epidermis and early appendageal buds. The buds continue to express matrilysin during mesenchymal invasion. As development progresses (15-19 weeks) matrilysin is concentrated only in cells at the distal portion of the invading follicular and sweat gland appendageal cords. In adult skin, matrilysin was localized specifically to the outer root sheath of the hair follicles and the secretory cells of the eccrine glands but was absent in the epidermis. Nodulocystic, keratotic, adenoid basal cell carcinomas (BCCs) did not express matrilysin. In contrast, in the more aggressive morpheaform (infiltrative) BCCs and recurrent BCCs, matrilysin was localized at the tumor-stromal interface. In squamous cell carcinomas matrilysin was present in tumor cells at the stromal interface surrounding the tumor nests. The demonstration of matrilysin protein in germinal basal cells during fetal skin development and its presence in tumor cells at the stromal junction suggests that this enzyme may contribute to the proteolytic activity associated with cell-extracellular matrix interactions during appendageal development and tumor invasion.
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PMID:Matrilysin (PUMP) correlates with dermal invasion during appendageal development and cutaneous neoplasia. 793 Jun 71

Matrilysin, which is a member of the matrix metalloproteinase family and is implicated in colon cancer invasion, is expressed in human colon adenocarcinoma-derived SW1116 cells. We investigated the effect of alpha-difluoromethylornithine (DFMO) on matrilysin expression in this cell line because others have shown that DFMO can inhibit invasion and carcinogenesis in epithelial tissues, including the colon, in experimental models. DFMO reduced extracellular levels of matrilysin protein after 4 d of treatment. Intracellular levels of matrilysin protein were minimally affected by DFMO treatment. The decrease in extracellular matrilysin protein levels caused by DFMO was not a consequence of lowered steady-state levels of matrilysin mRNA. After 4 d of exposure, the amount of this transcript was higher in DFMO-treated cells than in untreated cultures, whereas the mRNA stabilities were similar. These data show that polyamine depletion by DFMO can suppress the expression of matrilysin, a gene product thought to be involved in tumor invasion. The decrease in extracellular matrilysin protein caused by DFMO treatment appears to be due to a posttranscriptional mechanism, although transcription of this gene also seems to be affected by polyamines in SW1116 cells.
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PMID:Polyamine-dependent expression of the matrix metalloproteinase matrilysin in a human colon cancer-derived cell line. 794 2

The extra-cellular matrix (ECM) related antigens, type IV collagen, laminin, M(r) 68,000 laminin receptor (LR), M(r) 72,000 type IV collagenase (MMP-2), its inhibitor TIMP-2, and alpha 2-macroglobulin expression have been immunohistochemically investigated in 100 cases of human gastric carcinoma with a 5-yr follow up. Basement membranes were inversely related to tumoral differentiation. At the early intramucosal stage of both intestinal and diffuse histological types, TIMP-2 was expressed by the majority of tumor cells (60/63%), whereas MMP-2+ and LR+ cells were in the minority (24/19%, 23/0%, respectively). At the early submucosal stage, TIMP-2+ cells moderately decreased in both histological types (49/49%), whereas a consistently higher number of both MMP-2+ and LR+ cells were detected only in the diffuse carcinomas (72%). In the advanced stage, the expression of TIMP-2 further declined (22/24%), although the other two antigens increased or maintained high levels of expression. AMG+ cells never exceeded 10% in either histological type at any stage. In the liver metastases, both MMP-2+ and LR+ cells were more numerous than in the primary tumor (P < 0.002 and P < 0.01). Patients who died from their primary tumor had higher percentages of LR+, MMP-2+, and AMG+ cells and lower percentages of TIMP-2+ cells with respect to survivors. We believe evaluation of ECM-related antigens, and especially TIMP-2, may help determine a confident prognosis for gastric cancer.
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PMID:Prognosis of gastric carcinoma revealed by interactions between tumor cells and basement membrane. 800 47

The purpose of this study was to characterize stromal-epithelial interactions that result in induction of protease gene expression in squamous cell carcinoma of the skin. Coculture of the human squamous cell carcinoma cell line II4 with primary human foreskin fibroblasts was observed to induce mRNA expression of urokinase-type plasminogen activator (uPa), matrilysin, 92-kDa type IV collagenase, and c-ets, a transcriptional activator of several genes within the serine and matrix metalloprotease families. uPA and c-ets induction were localized to the fibroblast cell population. uPa induction was found to be dependent upon cell-cell contact with the tumor cell population, whereas c-ets induction was due to a combination of cell-cell contact and a tumor cell-derived soluble factor. In contrast, matrilysin induction localized to the tumor cells and was shown by Northern and Western analyses to occur in response to a fibroblast-derived soluble factor. These data demonstrate that both paracrine factors and cell-cell contact between stromal fibroblasts and epithelial tumor cells can influence protease gene expression.
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PMID:Paracrine factor and cell-cell contact-mediated induction of protease and c-ets gene expression in malignant keratinocyte/dermal fibroblast cocultures. 802 May 84


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