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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an effort to identify factors in primary tumors that would predict liver metastases, we retrospectively reviewed 102 patients with gastric cancer, and their tissue blocks were restained. New staining methods for elastin and endothelium were used to identify intratumoral vessels. Blood vessel invasion, thus detected, was analyzed quantitatively, as well as qualitatively, according to the location of invasion, the size of the involved vessel, and the mode of invasion. The invasion was then compared with the presence of liver metastasis by the chi 2 test, the Mann-Whitney U test, and the Student t test. Discrimination analysis of factors significantly correlated with liver metastasis was performed with linear discrimination function to identify a predictive model for liver metastasis. Significant differences in qualitative frequency of blood vessel invasion (p less than 0.01), the number of lymph node metastases (p less than 0.05), and the depth of tumor invasion (p less than 0.05) were found in those patients in whom liver metastasis developed, as compared with 5-year disease-free survivors. Quantitative analysis of blood vessel invasion revealed eight other factors correlated with liver metastasis; frequency of blood vessel invasion in the 0.01 to 0.1 mm and 0.1 to 1 mm diameter vessels, in the forms of complete, partial tumor thrombi, and vessel wall invasion, in the submucosa and the subserosa, and the number of anatomic stomach layers involved. Application of the discrimination coefficient to these factors allows prediction of liver metastasis with 81.8% sensitivity, 85.3% specificity, and 83.6% accuracy. Liver metastasis can be predicted from the qualitative and quantitative examination of blood vessel invasion within the primary tumor by the use of an elastic fiber stain.
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PMID:Blood vessel invasion in gastric carcinoma. 168 80

We have shown previously that an increase in tumor invasion and metastases occurred concurrently with a decrease in collagen content of the extracellular matrix surrounding the C3H mouse mammary adenocarcinoma borne by C3H/HeJ mice. In this paper we report the production of collagenase and elastase activities by the primary tumor cultures and three types of cloned C3H mouse mammary adenocarcinoma cell cultures. The primary tumor cell cultures and tumor-associated stromal cultures produced large amounts of collagenase and elastase activities. On the other hand, the primary tumor capsule cultures produced little or no collagenase and elastase activities even though they produced type I collagen. The production of proteases by the primary tumor cultures decreased along with time and with an alteration in the morphology of cell populations and/or passage of the cultures. The three clones of tumor cell cultures produced variable amounts of collagenase in response to induction by phorbol myristate acetate, an agent that stimulates maximal collagenase production. In contrast, all three cloned cultures elaborated significant amounts of elastase that degraded insoluble ligamental elastin, and most of the elastase production was increased further in response to induction by phorbol myristate acetate. Each cloned cell population exhibited differences in their production of collagenase and elastase in parallel with their difference in growth kinetics, yet these cells still possess the distinctive properties of the tumor. However, a unit amount of collagenase produced by each of the cloned cultures, with or without induction by phorbol myristate acetate, was less than that of the primary tumor cultures. Results suggest that some cell types or combination of cell types in the heterogeneous cell population of the tumor and/or their products appear to be responsible for the increased production of collagenase and elastase activities and for the invasiveness of a malignant tumor.
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PMID:Collagenase and elastase production by mouse mammary adenocarcinoma primary cultures and cloned cells. 302 19

The invasion of normal tissues and penetration of basement membranes by malignant cells is likely to require the active participation of hydrolytic enzymes. The four major groups of connective tissue proteins, glycoproteins, proteoglycans, collagen and elastin, vary in their quantitative distributions between different tissues. With the exception of elastin, they also vary qualitatively within each class, so that there are no 'typical' connective tissue barriers to tumor cell penetration. The matrix constituents are stabilized and organized by a variety of covalent and noncovalent interactions between the connective tissue proteins. These interactions play important roles in matrix integrity and may alter the susceptibilities of the constituents to degradative enzymes. It is likely that the complete degradation of the matrix will require the action of more than one enzyme because of differing susceptibilities to tissue proteinases. Primary and transplantable tumors produce well-characterized enzymes which may participate in invasion. These enzymes may also be involved in connective tissue turnover in other normal and pathological situations. The use of long-term tumor cell cultures has verified that tumor cells themselves are capable of producing these enzymes. However, there are many potential modulating influences operative in vivo which are absent in culture so that details of actual mechanisms and control of digestion of complex substrates are not well understood. Recent work on the degradation by tumor cells of extracellular matrices previously produced by cultured cells is likely to shed more light on pathways of tissue destruction in vivo. Experiments with tumor cell variants of defined metastatic potentials will also be useful, but invasive and metastatic abilities are not necessarily correlated. It is unlikely that simple correlations can be drawn between the production of one particular degradative enzyme by all tumor cells and the complex biological mechanisms operative during tumor invasion.
Cancer Metastasis Rev 1982
PMID:Extracellular matrix destruction by invasive tumor cells. 622 52

Collagenases are a family of metalloproteinases which may play a role in facilitating tumor cell invasion of the extracellular matrix. Tumor cells traverse two types of extracellular matrix: basement membranes and interstitial stroma, at multiple stages of the metastatic process. The matrix is a dense meshwork of collagen, proteoglycans, elastin and glycoproteins. Normally the matrix does not contain open spaces large enough for cell movement. Therefore numerous investigators have postulated that collagenolytic proteases, secreted by tumor cells or associated host cells, breakdown the extracellular matrix during tumor cell invasion. A large number of animal and human tumors have been shown to contain collagenase at a higher level than corresponding benign tissues. Separate collagenolytic metalloproteinases have been identified which degrade specific types of collagen. A basement membrane collagenolytic protease was shown to be elevated in a series of metastatic murine tumor cells. Immunologic studies using antibodies specific for collagenase have demonstrated that in vivo, tumor cells can produce collagenase. Therefore identification of collagenase in cultured lines of tumor cells is not an artifact of in vitro cultivation. In some cases, tumor cells may induce host cells to produce collagenase. The best evidence to date that collagenases actually play a role in invasion is derived from experiments in which natural collagenase inhibitors block tumor cell invasion of extracellular matrix in vitro.
Cancer Metastasis Rev 1982
PMID:Role of collagenases in tumor cell invasion. 630 68

Recent suggestions that tumor-cell targeting of elastin-rich tissues (e.g., lung) correlates with the presence of surface elastin receptors have been investigated. Receptors for insoluble (fibrous) elastin and for soluble elastin peptides have been implemented in these correlations. A rapid assay for binding of insoluble elastin has been devised. Two of the cell lines tested (M27 and MAT-LyLu), which metastasize to the lung, strongly bound fibrous elastin whereas a third (B16-F10) did not. None of 4 metastatic cell lines that do not target the lung (A549, 3LL, TA3, TA3-iso2) bound fibrous elastin. The ability of cell lines to interact with soluble elastin was tested by cell attachment to high-molecular-weight soluble elastin peptides adsorbed on a plastic surface. Three of 7 tested cell lines, B16-F10, M27 and TA3, attached to a soluble elastin coating. In contrast to the rapid binding of insoluble elastin particles, the cell interaction with immobilized soluble elastin peptides was delayed, suggesting that induction of receptors for soluble elastin and/or modification of the elastin coat was occurring. Thus, all 3 tested cell lines where metastases target the lung, namely, MAT-LyLu, B16-F10 and M-27, show soluble- or insoluble-elastin interactions, whereas, of 4 cell lines not targeting lungs, only one, TA3, reacts with soluble elastin.
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PMID:Binding of some metastatic tumor cell lines to fibrous elastin and elastin peptides. 838 30

Soluble kappa-elastin peptides were shown to stimulate the expression of MMP-2 (but not MMP-9) by human fibrosarcoma HT-1080 cells, both at the protein and mRNA levels; maximal effect being observed at a concentration of 25 microg/ml of kappa-elastin. The stimulatory effect could be reproduced using Val-Gly-Val-Ala-Pro-Gly (VGVAPG) peptide, an elastin-derived hydrophobic hexapeptide which represented the elastin receptor binding sequence of tropoelastin. Furthermore, treatment of cells with lactose (30 mM), which dissociated 67-kDa elastin binding protein (EBP) from cell surfaces, completely abolished this effect, suggesting that the elastin receptor could mediate such a response. Using a specific monoclonal antibody, 67-kDa EBP was detected in HT-1080 membrane preparations by Western immunoblotting. Following treatment with 25 microg/ml kappa-elastin or 200 microg/ml VGVAPG, increased levels of the active 62-kDa form of MMP-2 were found in HT-1080 cell extracts. Stimulation of MT1-MMP mRNA expression by treatment with elastin-derived peptides (EDPs) was shown by competitive polymerase chain reaction (PCR). A reverse zymography analysis revealed that EDPs also stimulated TIMP-2 (but not TIMP-1) production by HT-1080 cells. Competitive PCR confirmed increased TIMP-2 mRNA expression by such treatment. These results suggest that occupancy of the 67-kDa elastin receptor by elastin-derived peptides enhanced both expression and activation of proMMP-2 and consequently, could promote the invasive/metastatic ability of tumor cells expressing this receptor.
Clin Exp Metastasis 1998 Aug
PMID:Regulation of matrix metalloproteinase-2 (gelatinase A, MMP-2), membrane-type matrix metalloproteinase-1 (MT1-MMP) and tissue inhibitor of metalloproteinases-2 (TIMP-2) expression by elastin-derived peptides in human HT-1080 fibrosarcoma cell line. 987 97

HT-1080 fibrosarcoma cells express at their plasma membrane the elastin-binding protein (EBP). Occupancy of EBP by elastin fragments, tropoelastin or XGVAPG peptides was found to trigger procollagenase-1 (proMMP-1) overproduction by HT-1080 cells at the protein and enzyme levels. RT-PCR analysis indicated that elastin peptides did not modify the MMP-1 mRNA steady state levels, suggesting the involvement of a post-transcriptional mechanism. We previously reported that binding of elastin peptides to EBP induced other matrix metalloproteinases (MMP-2 and MT1-MMP) expression. Since those peptides were here found to also accelerate the secretion of urokinase from HT-1080 cells, culture medium was supplemented with plasminogen together with elastin peptides at aims to induce or potentiate MMPs activation cascades. In such conditions, plasmin activity was generated and exacerbate proMMP-1 and proMMP-2 activation. As a consequence, elastin peptides and plasminogen-treated HT-1080 cells displayed a significant type I collagen matrix invasive capacity.
Clin Exp Metastasis 2002
PMID:Cumulative influence of elastin peptides and plasminogen on matrix metalloproteinase activation and type I collagen invasion by HT-1080 fibrosarcoma cells. 1196 74

Malignant melanomas, which produce a large number of substances active in connective tissue modulation, must contend with the dermis to grow and propagate. We studied the morphologic interactions between tumorigenic malignant melanomas and dermal elastin. Formalin-fixed and paraffin-embedded tissues of 108 tumorigenic malignant melanomas were stained for elastic tissue with the Verhoeff-van Gieson method. Various aspects of the relationship between malignant melanoma and dermal elastin were analyzed in relation to the histologic and clinical data using univariate and multivariate analyses. Tumor thickness, mitotic rate, and the presence of elastin remnants within the tumors were found to be independent negative prognostic factors, the latter with borderline significance. Tumors with more remnants of elastin were associated with higher stage of disease and lymph node and distant metastases. Tumor infiltration between the elastic fibers in the tumor depth was associated with high Clark level, greater tumor thickness, high stage of disease, and lymph node metastases. At least partial preservation of elastic fibers in the tumor depth was a relatively good prognostic factor whereas complete absence of elastin was an adverse factor. Focal or multifocal absence of elastin in the midst of the tumors or in their depth was usually associated with lymphocytic infiltrates. We suggest that tumors with remnants of elastic fibers and/or invasion between elastic fibers in their depth may be fast growing and highly invasive. The absence of elastin within tumors and at their advancing edge may be related to the elaboration of elastin-degrading substances by melanoma cells or various inflammatory cells. Our findings indicate that the relationship between malignant melanomas and dermal connective tissue components, specifically elastin, may have prognostic significance.
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PMID:Relationship of tumorigenic malignant melanomas to dermal elastin: an expression of tumor/stromal interaction that may be related to prognosis. 1197 70

Cellular regulatory mechanisms normally maintain a delicate balance between cell proliferation, quiescence and death. The imbalance between these functions resulting from molecular intracellular changes is a key factor in tumorigenesis. Tumor cells detaching from the primary tumor possess a propension for invasion and metastasis formation. These tumor cells can attach, migrate, proliferate and grow in host tissue. The surrounding extracellular matrix (ECM) modulates these functions. It is now widely accepted that cell-matrix interactions play an important role in these processes. Most investigators concentrated their attention on the role of integrins in the above processes. There are, however, only scant data on the role of elastin and its receptors in tumor invasion. Nevertheless, experimental evidence indicates that the 67 kDa elastin-laminin receptor (ELR) subunit plays an important role in tumor invasion by mediating essential tumor cell functions leading to metastases. In this review we will concentrate on the putative role of the 67 kDa ELR subunit in tumor invasion.
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PMID:Putative role of 67 kDa elastin-laminin receptor in tumor invasion. 1208 52

Cutaneous melanoma is a highly malignant tumor type which is characterized by its tendency to give rise to metastases. Stromal relationships are essential for growth and metastasis of solid tumors. In cutaneous melanoma, microscopic level of invasion (Breslow index), overall architecture of cells (horizontal or vertical growth phase), angiogenesis, vessel invasion are morphological features which may carry prognostic significance. As demonstrated by in vivo studies, stromal reaction in melanoma is mainly characterized by collagen and elastin proteolysis preferentially localized around the tumor at the invasive front along with variable angiogenesis and lymphocyte infiltration. On the basis of recent findings, it becomes increasingly evident that resident stromal cells (fibroblasts, endothelial cells) are implicated in the metastatic process, including proliferation, matrix degradation, or migration of melanoma cells through cell-cell cross-talk by soluble factors (proteases, cytokines, growth factors) or by direct contact.
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PMID:Stromal reaction in cutaneous melanoma. 1503 66


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