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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases (MMP), such as 72 kDa type IV collagenase (MMP-2) and 92 kDa type IV collagenase (MMP-9), play an important role in tumor invasion and metastasis. Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) are specific inhibitors of MMP. To evaluate the expression of TIMP-1, TIMP-2, MMP-2, and MMP-9 in human colorectal cancer, surgical specimens of primary colorectal cancer (66 cases) and liver metastases (10 cases) were examined by Northern and dot-blot hybridization. The levels of TIMP-1, MMP-2 and MMP-9 mRNA were significantly higher in primary colorectal cancers than in their adjacent normal tissues, and those of the mRNAs for all four genes were significantly higher in liver metastases than in normal colorectal tissues. Higher levels of TIMP-1 mRNA were positively correlated with lymph node metastasis and the five-year survival, and higher levels of TIMP-1 and TIMP-2 mRNA were positively correlated with the Dukes classification. Our findings suggest that the expression of TIMP-1 and TIMP-2 is closely correlated with the progression of human colorectal cancer.
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PMID:Enhanced expression of tissue inhibitors of metalloproteinases in human colorectal tumors. 889 69

We have examined the expression of 2 tumor-associated metalloproteinases, MMP-2 and MMP-9, in 48 primary cultures of prostatic carcinoma (PRCA) and 33 cultures of benign prostatic hyperplasia (BPH). PRCA cultures secrete significantly more MMP-9 than their benign counterparts. Secreted MMP-2 did not differ significantly in cultures but was lower in PRCA cultures. Two cultures of benign origin exhibited high MMP-9 secretion and growth patterns consistent with a malignancy. Both cases were followed and successively re-evaluated histologically and rediagnosed as organ-confined PRCA. MMP expression in culture may be of predictive value in the identification of incidental PRCA. MMP-9 secretion and its ratio with MMP-2 were highest in epithelial cultures from invasive, metastatic tumors when compared both to disease confined to prostate gland and to locally extensive disease. MMP-9 secretion was greatest also in cultures derived from tissues of high Gleason histological grade. Active MMP-9 species were detected in 15 cultures (31%) of PRCA. Active MMP-2 species were observed in cultures of both BPH and PRCA origin in almost the same amounts. Although average levels were not significantly different, as a ratio to proform species, a significant elevation was observed in cultures of PRCA origin. We propose, therefore, that an elevated expression of MMP-9 and a high ratio of MMP-9 to MMP-2 in short-term prostate epithelial cultures is of potential diagnostic and prognostic significance.
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PMID:Increased matrix metalloproteinase-9 secretion in short-term tissue cultures of prostatic tumor cells. 890 Mar 72

The clinical behavior of giant cell tumors (GCTs) is unpredictable. To gain insight into this tumor's biological behavior, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were studied. These substances play essential roles in wound healing and neoplastic invasion and metastasis. Paraffin-embedded tissue was collected from 18 cases of histologically benign GCT, with 17 treated by curettage and 1 by resection. Eight cases showed no recurrence after a minimum of 2.5 years, and 10 had local recurrence. One showed metastasis. Antibodies to MMP-9, MMP-2, TIMP-1, and TIMP-2 were applied by immunohistochemical methods. In all cases, MMP-9 was strongly expressed in giant cells predominantly in a diffuse pattern and was strong but focal in stromal cells. MMP-2 decorated stromal cells and giant cells heterogeneously. TIMP-1 was variably expressed in giant cells of the nonrecurrent cases and was strongly present in a diffuse or patchy distribution in the stromal cells in 6 of 8 cases. However, in 9 of 10 recurrent cases, TIMP-1 was expressed weakly by both giant and stromal cells. TIMP-2 was variably expressed in the giant cells of the nonrecurrent cases, but 6 of 8 nonrecurrent cases showed strong stromal cell positivity for TIMP-2. Weak staining for TIMP-2 was observed in 7 of 10 recurrent cases in the stromal cells and 9 of 10 recurrent cases in the giant cells. These results indicate that expression of MMPs and TIMPs differs in giant cells and stromal cells in the same tumor. More significantly, in contrast to the nonrecurrent giant cell tumors, there is an imbalance in the MMPs and TIMPs in the recurrent tumors with a net excess of MMPs. This unopposed expression of MMPs in GCTs may play a role in breakdown of extracellular matrix and tissue invasion. Finally, these markers may prove useful in predicting behavior in these tumors.
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PMID:Expression of metalloproteinases and tissue inhibitors of metalloproteinases in giant cell tumor of bone: an immunohistochemical study with clinical correlation. 891 22

The proteolytic processes are thought to be the critical point in tumor invasion and metastasis, mainly by matrix metalloproteinases (MMPs) and serine proteases. We measured the activity of MMP-2 from 28 normal, 12 benign and 126 breast cancer tissues using gelatin zymography. Inactive MMP-2 (72 kD) was expressed in 53.6% of the normal and 66.6% of the cancer tissues, respectively (P = 0.77), while active MMP-2 (62 kD) was expressed in 28.6% and 73.0%, respectively (P = 0.003). The enzymatic activity of active MMP-2 (62 kD) measured in the gel band area was 4.0 +/- 7.2 mm2 in normal breasts, 7.7 +/- 9.8 mm2 in benign breast diseases, 9.5 +/- 8.5 mm2 in ductal carcinoma in situ (DCIS), and 12.0 +/- 13.7 mm2 in invasive cancers. The MMP-2 activation ratio (62 kD/62 kD + 72 kD) was 0.12 +/- 0.18 in normal tissues, 0.10 +/- 0.20 in benign diseases, 0.61 +/- 0.22 in DCIS, and 0.50 +/- 0.28 in invasive cancers. In conclusion, MMP-2 activation was the main cause of the increased 62 kD MMP-2 activity during the early phase of breast cancer, while production of MMP-2 supplemented the increased 62 kD activity in the late phase. We suggest, therefore, that these differential expressions of MMP-2 activation and production during the different stages of breast cancer progression are potential therapeutic targets for biological or gene therapy under the concept of stage-oriented cancer treatment.
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PMID:Sequential activation and production of matrix metalloproteinase-2 during breast cancer progression. 897 May 81

Oligodeoxyribonucleoside methylphosphonates (d-OMP) were synthesized whose sequences are complementary to sequences found in the mRNA coding for the 72-kDa (MMP-2) or 92-kDA (MMP-9) forms of human collagenase i.v., matrix metalloproteinases (MMP) whose excessive secretion correlates with the metastatic potential of tumor cells. The effects of these oligomers on MMP-2 and MMP-9 activities secreted by HT1080 cells, a human fibrosarcoma cell line, were studied using a gelatin zymography assay. A d-OMP, M2.3, complementary to nucleotides 14 to 28 of the initiation codon region of MMP-2 mRNA selectively inhibited MMP-2 activity, whereas a d-OMP, M9.1, which was targeted to nucleotides -19 to -5 of the 5'-untranslated region of MMP-9 mRNA selectively inhibited MMP-9 activity over the concentration range 5-50 microM. At 100 microM concentration, both M2.3 and M9.1 inhibited the activities of both MMP-2 and MMP-9. These oligomers were completely stable under cell culture conditions and did not appear to adversely affect cell growth after 48 hours at concentrations up to 100 microM, although 100 microM M9.1 did reduce cell growth 30% after prolonged, 120-hours exposure. Other d-OMP tested either had no effect on collagenase activity or inhibited both MMP-2 and MMP-9 activities. The latter oligomer was complementary to MMP-2 mRNA and partially complementary to MMP-9 mRNA. Oligomer M2.3 was also tested for its effects on the morphology of malignant human lung cells, BZR-T33, growing on the surface of reconstituted base membrane, Matrigel, in culture. In absence of oligomer, the BZR-T33 cells formed extensive networks indicative of the ability of the cells to invade the Matrigel substrate. In the presence of 100 microM M2.3, BZR-T33 formed colonies of rounded cells, a morphology typical of noninvasive cells. Other non-complementary d-OMP had no effect on the morphology of BZR-T33 under these conditions. These results suggest that antisense d-OMP may be useful for inhibiting expression of collagenase in human tumor cells and for studying the role of collagenase expression in tumor cell metastasis.
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PMID:Inhibition of human collagenase activity by antisense oligonucleoside methylphosphonates. 901 63

Pancreatic islets contain trace amounts of zinc to form insulin dimer, and matrix metalloproteinases (MMPs) are single-chain zinc-containing metallo-enzymes. By immunocytochemically staining pancreatic tissue, which contained exocrine duct adenocarcinoma, normal islets were incidentally found positive for gelatinase-A (MMP-2) and gelatinase-B (MMP-9), and for tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2). Normal islets from five pancreata were exclusively stained for two each of gelatinases and TIMPs. Twenty-two islet cell tumors were also stained for pancreatic hormones, gelatinases, and TIMPs, which included insulinomas, gastrinomas, glucagonomas, pancreatic polypeptide-omas (PPomas), and nonfunctioning tumor. In general, islet cell tumors were weakly stained for gelatinases and TIMPs, compared with normal islets in the adjacent pancreatic tissue. No clear difference in staining intensity among five kinds of islet cell tumors was observed. The selective immunolocalization of gelatinases and TIMPs in islet cells and islet cell tumors may suggest possible a structure-function relationship among zinc, gelatinases-TIMPs, and pancreatic hormones.
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PMID:Gelatinases and inhibitors of gelatinases in pancreatic islets and islet cell tumors. 902 26

Membrane-type matrix metalloproteinase 1 (MT1-MMP) has been recently described as an activator of proMMP-2 (MMP-2) which is involved in tumor invasion. We have shown by in situ hybridization that MT1-MMP is produced by stromal cells in close contact to preinvasive and invasive tumor cells of breast carcinomas. Of particular interest was the observation that some fibroblasts express this enzyme in focal areas in preinvasive lesions, suggesting that particular tumor cells may stimulate fibroblasts to produce MT1-MMP. We have therefore compared the ability of two different breast cancer cell lines, one non-invasive (MCF7) and one invasive (MDA-MB-231) to stimulate MT1-MMP production in human fibroblasts with consequent proMMP-2-activation. The MDA-MB-231 conditioned medium induced MT1-MMP mRNAs in human fibroblasts and a parallel activation of proMMP-2 whereas MCF7 conditioned medium did not have any effect. These results suggest the existence of soluble factor(s) secreted by invasive or some preinvasive breast tumor cells which stimulate fibroblasts to produce and activate MMPs, and emphasize the cooperation between cancer and stromal cells in tumor invasion.
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PMID:Induction of membrane-type matrix metalloproteinase 1 (MT1-MMP) expression in human fibroblasts by breast adenocarcinoma cells. 906 92

Destruction of the basement membrane (BM) is mandatory for tumor spread, and matrix metalloproteinases (MMPs) are known to be implicated in colon cancer invasion and metastasis by digesting type IV collagen, a main component of the BM. The current study analyzed the expression of MMP-2 and MMP-9 in pancreatic cancer tissues. Frozen specimens of pancreatic cancer (n = 10), a liver metastatic nodule from pancreatic cancer (n = 1), and normal pancreas (n = 3) were homogenized and analyzed by zymography. The activated form of MMP-9 (82 kDa) was detected in all of the normal and malignant tissues, while the activated form of MMP-2 (62 kDa) was detected in all of the pancreatic cancers and its metastatic tissue, but not in the normal pancreatic tissues. These results indicate that expression of the activated form of MMP-2 may be specific to pancreatic cancer, while that of MMP-9 may be unrelated to it.
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PMID:Detection of matrix metalloproteinase activity in human pancreatic cancer. 908 44

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes implicated in the invasion and metastasis of many cancers. In situ hybridization techniques were used to reveal sites of expression of collagenase (MMP-1), gelatinase 72 kd (MMP-2), gelatinase 92 kd (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in head and neck carcinomas (N = 21). Both TIMP-1 and gelatinase 72 kd were expressed in nearly all tumors, whereas the expression of collagenase and gelatinase 92 kd showed variability. Tumor-associated expression of MMPs was strongest in stromal cells near advancing margins. No differences in expression levels were detected between primary and metastatic sites. This paper reviews the literature and discusses the significance and possible implications of MMPs in head and neck squamous cell carcinoma.
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PMID:Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in head and neck squamous cell carcinoma. 910 15

Human collagenase-3 (MMP13) is a recently identified member of the matrix metalloproteinase (MMP) family that is expressed in breast carcinomas and in articular cartilage from arthritic patients. In this work we have isolated and characterized genomic clones coding for human collagenase-3. This gene is composed of 10 exons and 9 introns and spans over 12.5 kb. The overall organization of the collagenase-3 gene is similar to that of other MMP genes clustered at chromosome 11q22, including fibroblast collagenase (MMP-1), matrilysin (MMP-7), and macrophage metalloelastase (MMP-12), but is more distantly related to genes coding for stromelysin-3 (MMP-11), gelatinase-A (MMP-2), and gelatinase-B (MMP-9), which map outside of this gene cluster. Nucleotide sequence analysis of about 1 kb of the 5'-flanking region of the collagenase-3 gene revealed the presence of a TATA box, an AP-1 motif, a PEA-3 consensus sequence, an osteoblast specific element (OSE-2), and a TGF-beta inhibitory element. Transient transfection experiments in HeLa and COS-1 cells with chloramphenicol acetyltransferase (CAT)-containing constructs showed that the AP-1 site is functional and responsible for the observed inducibility of the reporter gene by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). However, and in contrast to other MMP genes, no significative synergistic effect on CAT activity between the AP-1 and PEA-3 elements found in the collagenase-3 gene promoter was found. DNA binding analysis with nuclear extracts from HeLa cells revealed the formation of specific complexes between collagenase-3 promoter sequences containing the AP-1 site and nuclear proteins. The presence of this AP-1 functional site, which is able to confer responsiveness to a variety of tumor promoters and oncogene products, amy contribute to explaining the high-level expression of collagenase-3 in breast carcinomas and degenerative joint diseases.
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PMID:Structural analysis and promoter characterization of the human collagenase-3 gene (MMP13). 911 88


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