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)

Human prostate cancer displays a high degree of variability in its rate of spread, which could be due largely to differences in the invasive potential of the tumor cells. The degradation of the basal lamina and stromal extracellular matrix is mediated in part by the secretion of matrix metalloproteinases (MMPs). Matrilysin (PUMP-1, MMP-7) and gelatinase A (M(r) 72,000 type IV collagenase, MMP-2) have been shown to be overexpressed in prostate carcinoma. We have expressed the single MMP matrilysin in the tumorigenic but nonmetastatic human prostate tumor cell line DU-145 to determine if matrilysin has a functional role in prostate tumor cell invasion. DU-145 cells expressing matrilysin were significantly more invasive than vector-only transfected cell lines as assayed by a severe combined immunodeficient mouse model of tumor cell invasion. Vector-only transfected DU-145 cells injected i.p. into severe combined immunodeficient mice invaded the diaphragm in only 1 of 9 mice (11%), whereas matrilysin-transfected DU-145 cells invaded the diaphragm in 12 of 18 mice (66%). The difference between the controls and matrilysin-transfected cells was statistically significant (P < 0.006). These results suggest a functional role for matrilysin in the initial invasion of prostate cancer through the epithelial basal lamina and into the surrounding stroma.
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PMID:Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice. 841 33

The expression of MMP-7 (pump-1) gene was examined in 10 cases of colorectal cancer by utilizing RT-PCR. In 9 out of 10 cases, MMP-7 mRNA was detected in cancerous tissue, whereas none was detected in adjacent normal colon tissue. However, this message was detected in only 1 out of 6 colon-cancer cell lines. In colonic mucosa from 3 patients with ulcerative colitis it was not detected. The expression of MMP-2 (72-kDa type-IV collagenase) mRNA was also investigated in the same tissue samples, and was detected in all samples, including cancerous and non-cancerous tissue. Our data suggest that MMP-7 is expressed in a tumor-associated manner in colorectal cancers and may play a role in tumor progression.
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PMID:Expression of MMP-7(PUMP-1) mRNA in human colorectal cancers. 851 52

The 72 kDa type IV collagenase (gelatinase), a matrix metalloproteinase (MMP-2), has been proposed to potentiate the invasion and metastasis of malignant tumors. To determine the potential role of the MMP-2 in human gliomas and normal brain tissue, we examined the relative amounts of protein, mRNA, and distribution. Using gelatin zymography, densitometry, and an enzyme-linked immunosorbent assay for the quantitative determination of the MMP-2, we found that the enzyme's activity was significantly elevated in malignant astrocytomas, especially in glioblastoma multiforme, compared to low-grade glioma and normal brain tissues. As determined by Northern blot analysis, the amount of MMP-2 mRNA transcript was higher in anaplastic astrocytomas and glioblastoma multiforme tumors than in normal brain tissues or low-grade gliomas, a finding that was consistent with the amounts of MMP-2 protein detected in these tissues. Immunohistochemical studies demonstrated that MMP-2 was localized in tumor cells and vasculature cells of malignant astrocytomas. Staining intensity was clearly lower in low-grade astrocytomas, and immunoreactivity was very low or undetectable in normal brain astrocytes. The results suggest that expression of the MMP-2 is dramatically upregulated in malignant gliomas, correlating with the malignant progression of human gliomas in vivo.
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PMID:Expression and localization of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo. 852 15

MMP-2 (gelatinase A) has been associated with the invasive potential of many cancer cells both in vitro and in vivo. It is now becoming clear that the activation of this enzyme might be a key step in tumor invasion. This activation process has been shown to be a membrane-associated pathway inducible by various agents such as collagen type I, concanavalin A or TGF-beta, but its physiological regulation is still largely unresolved. MT-MMP was recently discovered and described as a potential gelatinase-A activator. In the present study, we investigated the expression of MT-MMP (membrane-type metalloproteinase) in cervical cancer cells both in vitro and in vivo. Comparing several in vitro-transformed cervical cell lines, previously shown to display different invasive potentials, our results showed that the ability of cells to overexpress MT-MMP mRNA following ConA induction correlated with their ability to activate gelatinase A and with a highly invasive behavior. Moreover, using immunohistochemistry and in situ hybridization, we found a higher level of MT-MMP expression in invasive cervical carcinoma and lymph node metastases compared to its expression in non-invasive CIN III lesions. Our in vivo observations also clearly demonstrated a cooperation between stromal and tumor cells for the production of MT-MMP. Taken together, our results clearly correlated high level MT-MMP expression with invasiveness, and thus suggested that MT-MMP might play a crucial role in cervical tumor invasion.
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PMID:High level of MT-MMP expression is associated with invasiveness of cervical cancer cells. 856 19

We examined the production and tissue localization of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in gastric carcinoma tissues. MMP-1 (tissue collagenase), MMP-9 (gelatinase B) and TIMP-2 were immunolocalized in carcinoma cells and MMP-2 (gelatinase A) on tumor cell membranes, whereas no or little immunostaining for MMP-3 (stromelysin-1) and TIMP-1 was seen in carcinoma cells. Stromal cells in carcinoma tissue were also positively stained for these MMPs and TIMPs. MMP-2 immunostaining was observed exclusively on advanced gastric carcinoma cells and correlated with vascular invasion by tumor cells. Sandwich enzyme immunoassays revealed enhanced production of MMP-1, MMP-2, MMP-3, MMP-9 and TIMP-1 by carcinoma tissues. Gelatinolytic activities were significantly higher in carcinoma samples than in normal controls. Using gelatin zymography, active forms of MMP-2 and MMP-9 were more frequently detected in carcinoma tissue, and the activation rate of the zymogen of MMP-2 (proMMP-2), but not that of proMMP-9, correlated well with degree of local invasion and lymphatic permeation. Our data indicate an enhanced production of 4 MMPs in gastric carcinoma tissue and suggest that activation of pro-MMP-2 may be a key step for spreading of gastric carcinoma cells.
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PMID:Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (gelatinase A) in human gastric carcinomas. 860 68

The matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) have been associated with tumor invasion and metastasis in many human cancers. Immunohistochemical studies were performed on frozen tumor samples from 42 patients with invasive bladder cancer treated by cystectomy with monoclonal antibodies against the Mr 72,000 gelatinase A (MMP-2), Mr 92,000 gelatinase B (MMP-9), and TIMP-2 to evaluate their significance in bladder cancer. Immunoreactivity for the gelatinases was predominantly tumor cell-associated, whereas strong TIMP-2 staining was mostly detected in the stroma. Tumor cells demonstrated moderate to strong reactivity for MMP-2 and MMP-9 in 71 and 71% of cases, respectively, which did not correlate with stage, grade, or outcome. Tumor cells were positive for TIMP-2 in 26 (62%) of 42 cases, and this correlated with a worse outcome (69 versus 25% died of disease; P < 0.05). In 31 (74%) of 42, there was moderate to strong stromal staining for TIMP-2; this also was associated with a poor outcome (65 versus 25% died of cancer; P < 0.05). Tumor basement membrane (BM) status was investigated using an antibody to type IV collagen. In 9 cases, the invasive tumor nests were surrounded by an intact BM; in 7 of these, stromal staining for TIMP-2 was absent. None of these 9 patients (0%) died of tumors compared with 7 (100%) of 7 with complete loss of BM staining (P < 0.001). These results suggest a potential role for TIMP-2 and BM staining as prognostic indicators in invasive bladder cancer.
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PMID:High levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) expression are associated with poor outcome in invasive bladder cancer. 860 16

We examined the anti-invasive activity of ursolic acid (UA) on the highly metastatic HT1080 human fibrosarcoma cell line. UA reduced tumor cell invasion through a reconstituted basement membrane in a transwell chamber. A significant down-regulation of matrix metalloproteinase-9 [MMP-9; Mr 92,000 gelatinase/type IV collagenase (gelatinase B)] by UA was detected by Northern blot analysis. However, MMP-2 [Mr 72,000 gelatinase/type IV collagenase (gelatinase A)] and membrane-type MMP were constantly expressed, and the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 also was not changed after 3 and 6 days of treatment with UA. Quantitative gelatin-based zymography confirmed a markedly reduced expression of MMP-9 but not MMP-2 after treatment with UA. To confirm the UA-induced down-regulation of MMP-9 expression, we constructed a secreted alkaline phosphatase (SEAP) reporter vector including MMP-9 promoter. After transfection of MMP-9/SEAP reporter vector into HT1080 cells, reduced SEAP activity was detected after treatment with UA. These results suggest that down-regulation of MMP-9 contributes to the anti-invasive activity of UA in HT1080 cells.
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PMID:Anti-invasive activity of ursolic acid correlates with the reduced expression of matrix metalloproteinase-9 (MMP-9) in HT1080 human fibrosarcoma cells. 862 99

Although hypoxic cells are generally resistant to radiation and chemical therapies designed to halt the spread of neoplastic disease, few investigations have been carried out with regard to the molecular mechanisms responsible for this phenomenon. Here, we report of the development of an in vitro model system with which to study the molecular mechanisms involved in the proliferation and invasion of human ovarian carcinoma cells under hypoxia. Results from [(3)]thymidine incorporation experiments indicate that hypoxia triggers cessation of ovarian carcinoma cell DNA synthesis. Flow cytometry analysis of cellular DNA content for hypoxic cultures revealed that cell cycle progression was arrested. This arrest was found to be reversible upon reoxygenation of the cultures. Concomitant with this growth arrest is hypophosphorylation of pRB and a reduction in cyclin A abundance, suggesting that hypoxia induces growth arrest by regulating the activities of these crucial cell cycle-regulatory proteins. In vitro invasion assays revealed that hypoxia has no appreciable effect on the invasive ability of these cells. Immunoblotting established that the detected proteolytic activity was due to the matrix metalloproteinase MMP-2, the M(r) 72,000 type IV collagenase that is most closely associated with the metastatic phenotype in vitro and in vivo. These data support the notion that populations of ovarian carcinoma cells are capable of surviving and invading extracellular matrix during hypoxic conditions and, after a more suitable oxygen environment is reached, giving rise to new cell colonies.
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PMID:Hypoxia arrests ovarian carcinoma cell cycle progression, but invasion is unaffected. 864 Jul 79

Biological effects of sex steroids (estradiol-17beta, E2; progesterone, P; medroxyprogesterone acetate, MPA; Danazol, DZ) and growth factors (epidermal growth factor, EGF; transforming growth factor, TGF-alpha,beta) on migration and invasion of endometrial adenocarcinoma SNG-M cells were investigated by haptotactic migration and haptoinvasion assay. The enzymatic degradation of the extracellular matrix by tumor cells was also examined. Tumor cell migration along a gradient of substratum-bound fibronectin was inhibited by 0.1-10 microM MPA and DZ, but promoted by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. E2, P and TGF-beta did not have any effect on the motility of tumor cells. These effects were also confirmed by wound assay. The invasive activity of SNG-M cells into reconstituted basement membrane (Matrigel) was inhibited by the presence of 0.1-10 microM MPA and DZ, but promoted by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. E2, P and TGF-beta did not have any effect on tumor cell invasion. The zymography of tumor-conditioned medium showed that the treatment of SNG-M cells with EGF and TGF-alpha resulted in the increase of the 68, 72 and 92 kDa type IV collagenases (matrix metalloproteinase, MMP-2 and 9). Sex steroids and TGF-beta did not have significant effects on MMP-2 and 9. Stromelysin (MMP-3), also secreted by SNG-M cells, was not affected by sex steroids and growth factors. These results suggest that EGF and TGF-alpha act as positive regulators on the invasion process of endometrial adenocarcinoma cells, which may partly be associated with the induction of type IV collagenase secretion by tumor cells. The inhibitory effects of MPA and DZ on tumor cell invasion may depend at least partly on their inhibitory action on the motility of tumor cells.
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PMID:Effects of sex steroids and growth factors on migration and invasion of endometrial adenocarcinoma SNG-M cells in vitro. 864 91

The major obstacle towards improved survival from gastric cancer is in the development of metastatic disease. Techniques in cellular and molecular biology have now advanced to the point to allow an examination of specific biomolecules in processes related to gastric cancer cell invasion through the basement membrane of blood vessels or lymphatics (eg, the first step in developing metastatic disease). Identification of such biomolecules in primary gastric cancer has been enhanced by the establishment of primary human gastric cancer cell lines. These cell lines, named SK-GT for Sloan-Kettering gastric tumor, have provided the basis for a detailed analysis of the invasive phenotype of gastric cancer cells and has resulted in the identification of potentially important prognostic biomarkers. These molecular studies have revealed that in gastric cancer cells there exists a series of integrated biomolecules that are intimately involved in processes related to tumor cell invasion. Included among these are proteins associated with attachment to the basement membrane (ie, laminin receptor) as well as with proteolysis of the basement membrane (ie, matrix metalloproteinase-2, MMP-2). These factors, as well as others, have been clinically evaluated for their prognostic significance in patients with resected, primary gastric cancer. These clinical studies indicate that overexpression of factors associated with the invasion of gastric cancer cells through the basement membrane, including E-cadherin, MMP-2, plasminogen activator inhibitor-1 (PAI-1), and tissue inhibitor metalloproteinase-2 (TIMP-2), can be predictive of tumor recurrence and overall survival in patients with this disease.
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PMID:Invasion and metastases in gastric cancer: in vitro and in vivo models with clinical correlations. 865 15


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