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

Regulation of a number of adhesion molecules during neural crest cell migration was studied. The neural crest, a transient embryonic neural epithelium structure, undergoes mesenchymal transformation (epithelial-mesenchymal transition). The cells then migrate, giving rise to a variety of elements including the peripheral nervous system and melanocytes. During migration, neural crest cells do not express functional cell Adhesion Molecules but interact specifically with cell-binding domains in fibronectin molecules. A rat bladder carcinoma cell line was used as an in vitro model to study conversion of epithelial cells to a migratory fibroblast-like state. Conversion can be induced by culture on collagen or exposure to acidic Fibroblast Growth Factor (aFGF). Furthermore, constitutive fibroblast-like transformation can be induced by transfection with cDNA encoding aFGF. Growth factor-producing clones exhibit increased invasive and metastatic properties as compared with non-FGF-producing control cells. This model may provide increased understanding of the role of the different adhesion molecules in processes involving cell remodeling, such as tumor spread and development of metastases.
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PMID:[Adhesion and mobility of embryonic and tumoral cells]. 128 12

A human prostate cancer model was established by inoculating a prostate specific antigen (PSA)-producing LNCaP cell line with either prostate or bone fibroblasts. Alternatively, this human prostate cancer model can also be established by inoculating LNCaP cells with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam. The resulting LNCaP tumors were used to evaluate PSA production and excretion in athymic hosts. This model was also employed to examine the biochemical nature of mesenchymal cell-derived growth-promoting protein(s) and to assess the efficacy of potential chemotherapeutic agents. Because of the propensity of human prostate cancer to metastasize to the bone, this study defined a 1.0 M NaCl-eluted fraction, MS1, from the conditioned medium of a bone stromal cell line (MS) by heparin-affinity column chromatography. The growth-promoting activity was assayed both in vivo (e.g., tumor formation) and in vitro (e.g., soft agar colony formation). We found that the growth-promoting activity was trypsin- and heat-sensitive, and partially degraded by acid and dithiothreitol. Immunochemical studies indicated that the polyclonal antibody raised against MS1 blocked the growth-promoting effect elicited by the bone-conditioned media. This growth-promoting factor was found to be immunochemically dissimilar to KGF, HGF, and bFGF. However, addition of bFGF, HGF and NGF, but not aFGF, TGF beta, IGF1, IGF2, PDGF, EGF, TGF alpha and KGF, stimulated anchorage-independent growth of prostate cells, a condition closely parallel to tumor formation in vivo. We found that the MS1 fraction also contained fibronectin and tenascin but not laminin or collagen IV.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human prostate cancer model: roles of growth factors and extracellular matrices. 128 80

The invasiveness of human gastric carcinoma cell lines (MKN45 and MKN28) in the subcutaneous tissue of nude mice and the degrading capacities of extracellular matrix (ECM) were studied. MKN45 cells were more invasive than were the MKN28 cells. Immunostaining revealed dense lamellar accumulation of fibronectin (FN) around the tumors. Along the front of the invasive MKN45 growth, however, the FN fibers were discontinuous and/or had completely vanished; the MKN28 tumor showed no FN fiber disconnection. ECM components other than FN never displayed such peritumoral massive accumulation. Cocultivation of human fibroblasts with MKN45 cells, more evidently than with MKN28 cells, revealed degradation of FN produced by fibroblasts in contact with each tumor. Both cell lines produced several FN-degrading enzymes in serum-free cultures. Proteases from the MKN45 medium were more active than were those of MKN28 in urokinase-type plasminogen activator (uPA) and metal-dependent serine proteinase-like proteases of 75 and 68 kDa in molecular weight (MW). Type I collagen-degrading 48-kDa protease was also detected from MKN45 medium but not from the MKN28 medium. MKN28 cells secreted other kinds of FN-degrading enzymes, estimated at approximate MWs of 29 and 100-150 kDa. We found no distinct differences in capacity to produce ECM components or ability to adhere to purified ECM components between these two cell lines. From these results we conclude that the stromal invasion of these cells into the subcutaneous tissue of nude mice is profoundly related to their FN-degrading capability. This capability may be catalyzed by uPA and/or metal-dependent serine proteinase-like proteases of 75 and 68 kDa.
Invasion Metastasis 1992
PMID:Fibronectin degradation by human gastric carcinoma cell lines and its associated proteases in relation to stromal invasion in nude mice. 129 40

We examined the fibronectin-adhesive properties of clones from a rat colonic cell line exhibiting distinct tumorigenicity in a syngeneic host. These cells were originally selected on the basis of differential adhesion to plastic surfaces. The TR cell line, when injected subcutaneously, forms a tumour which grows progressively and gives off metastases, whereas the TS cell line forms a small tumour which regresses within a few weeks. The regression is largely mediated by immunological factors and involves a fibroblastic reaction. REGb, a clone from the TS subline, adhered better to fibronectin or RGDS tetrapeptide than did PROb, a clone from the TR subline. However, there was little binding to the RGD tripeptide with either clone. The degree of adhesion was dependent on time and substrate concentration. After 6 h of incubation, 38% and 55% respectively of PROb and REGb cells bound to plates coated with 10 micrograms/ml fibronectin. Adhesion of both clones to fibronectin was inhibited to various degrees when cells were preincubated with RGDS, GRGDS or GRADSPK peptides, whereas other synthetic peptides such as RGD, GRGD or GRGFSPK were ineffective. Binding experiments using 125I-labelled fibronectin showed 39,000 fibronectin receptor sites on REGb cells but only 17,000 on PROb cells. Flow cytometry analysis using both anti-alpha 5 and anti-beta 1 integrins showed more fibronectin receptor sites on REGb than on PROb cells. Both approaches were in accordance with the higher adhesiveness of the REGb clone to fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential adhesion of rat colon carcinoma cells to fibronectin in relation to their tumorigenicity. 130 47

Cells of an adherent subline (74AD, adhesion greater than 95%) and a floating subline (74FL, adhesion less than 1%) of rat ascites hepatoma AH7974 produced substrates containing fibronectin (FN), laminin (LN) and type IV collagen (CL-IV), with 74AD cells producing higher levels of each component. 74AD cells possessed high adhesion affinities to LN and CL-IV substrates. By contrast, 74FL cells hardly adhered to these purified attachment proteins. The difference in adhesion between the two lines in vitro tended to increase on incubation of the cells in medium containing fetal bovine serum. However, 74FL and 74AD cells adhered avidly to the extracellular matrix (ECM) of vascular endothelial cells. Although the cell-ECM adhesion apparently was not inhibited by pretreatment of the ECM with anti-FN, anti-LN and anti-CL-IV antibodies, the 74FL cell-ECM adhesion was inhibited considerably by pretreatment of the ECM with a mixture of these antibodies, especially with a combination of anti-FN and anti-LN antibodies. The lung-colonizing potential of 74FL cells was greater than that of 74AD cells, but the liver-colonizing potential of 74FL cells was less than that of 74AD cells. These results suggest that rat ascites hepatoma cells with extremely reduced substrate adhesiveness retain an adhesion mechanism that binds to FN and LN in the ECM of vascular endothelial cells. This mechanism may be a minimum essential unit of tumor cell-ECM adhesion in lung colonization, but the unit is insufficient for liver colonization of these cells.
Clin Exp Metastasis 1992 Jul
PMID:Substrate adhesiveness and experimental metastatic potential of rat ascites hepatoma AH7974-derived variant sublines. 137 14

Tenascin is a fibroblast product and extracellular matrix protein probably excerting a fibronectin-antagonizing role. Tenascin is broadly distributed interstitially during embryogenesis but restricted to a small range of structures in normal adult tissues. Using tenascin antibodies and an indirect immunoperoxidase method, normal colon, colitis, colon adenomas, and colorectal carcinomas were examined for tissue distribution of tenascin. Normal mucosa displayed a sparce meshwork of microfibrillar tenascin in the lamina propria. The basement membrane was tenascin negative at the bottom of the crypt and developed into a positive band steadily broadening towards the mucosal surface. In colitis, this polarity was effaced; the basement membrane was a broad tenascin-positive band nearly throughout while interstitial tenascin was moderately increased. Loss of polarity in tenascin content of the basement membrane was a constant feature of adenomas, inconsistently paralleled by structural alterations in surface qualities and continuity of tenascin pattern of the basement membrane. These were most pronounced in carcinomas, where this interface was often discontinuous and had a rough surface; in addition, interstitial tenascin was considerably increased. In carcinomas, the rough surface aspect of the tenascin pattern of the basement membrane was correlated with presence of lymph node metastases (P = 0.04). It is concluded that alterations in tenascin pattern and content reflect complex disturbances in the interaction of inflamed/neoplastic colon epithelium and underlying matrix, leading to an organoid induction of tenascin in the inflammatory context and to induction together with structural abnormalities in neoplasia.
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PMID:Altered content and distribution of tenascin in colitis, colon adenoma, and colorectal carcinoma. 137 2

Human melanoma is a highly metastatic cancer and the regional lymph nodes are generally the first site of metastasis. Adhesion to cryostat sections of human lymph nodes was therefore studied using two human melanoma models established from lymph node metastases, namely, MeWo cell lines of diverse metastatic potentials and a highly metastatic cell line of recent origin designated MIM/8. We found a good correlation between the metastatic potentials of the melanoma cells as measured in nude mice and their ability to adhere to cryostat sections of human lymph nodes. When adhesion to immobilized extracellular matrix proteins was measured, a significant increase in adhesion, which correlated with increased metastasis, was seen mainly on vitronectin and to a lesser extent on fibronectin. The adhesion to vitronectin and to the frozen sections were specifically blocked by an RGD-containing peptide, mAb 661 to vitronectin and mAb LM609 to integrin alpha v beta 3. FACS analysis revealed a significant and specific increase in cell surface expression of alpha v beta 3 on the metastatic cells as compared to the parent line. Together these results suggest that the adhesion of melanoma cells to lymph node vitronectin via the alpha v beta 3 receptor plays a role in the process of lymphatic dissemination.
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PMID:Human melanoma cells derived from lymphatic metastases use integrin alpha v beta 3 to adhere to lymph node vitronectin. 138 72

A recognized model of tumor invasion requires cells to adhere to epithelial basement membrane and extracellular matrix components triggering release of proteases thus allowing cancer cells to invade the substrate. This adhesion is mediated by beta 1 integrins, a family of receptors to substrates such as collagen, laminin, and fibronectin. In order to study tumor invasion in follicular thyroid cancer (FTC), we used cell lines derived from a single patient's FTC primary tumor (FTC-133), neck lymph node metastases (FTC-236), and lung metastases (FTC-238). In vitro invasion as determined by the ability of the tumor cells to penetrate Matrigel was assessed by scanning electron microscopy. FTC-133 did not invade, FTC-236 was moderately invasive, and FTC-238 was highly invasive. Immunoprecipation with a monoclonal antibody to beta 1 integrin subunits and SDS-PAGE showed increased synthesis and flow cytometry showed increased expression of this subunit in FTC-236 and FTC-238 compared to FTC-133. Proteolytic activity was assessed by gelatin zymography. FTC-238 cell extract and conditioned media exhibited a more complex array of proteases consistent with activated type I collagenase and stromelysin compared to the less invasive clones, however 72 and 92 kd gelatinases consistent with type IV collagenases were present in the conditioned media from all three lines. In conclusion, in vitro invasion parallels in vivo metastasis by the source cells in the FTC-133/236/238 cell-lines. The ability to invade basement membrane preparation correlates with increased synthesis and expression of beta 1 integrins and activation of tumor proteases.
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PMID:Invasion by cultured human follicular thyroid cancer correlates with increased beta 1 integrins and production of proteases. 138 45

Thrombospondin (TSP) is a 450 kDa adhesive glycoprotein. It is present in high concentrations in the platelet alpha-granule and can readily be secreted following platelet activation where local concentrations can be increased by 3-4 orders of magnitude. TSP is also synthesized by a variety of other cells and is incorporated into their extracellular matrix. TSP is a homotrimer with a number of functional domains, at least four of which might serve as receptor recognizing regions. The amino-terminal heparin binding domain interacts with heparin, other glycosaminoglycans and glycolipids and likely recognizes specific cell surface proteoglycans. The central disulfide cross-linked region, 210 kDa non-reduced and 70 kDa reduced, contains a peptide motif CSVTCG which is apparently responsible for binding to glycoprotein IV (CD36) with high affinity. Immediately adjacent to the calcium binding region of TSP, which undergoes considerable molecular relaxation in the absence of calcium, is an RGDA sequence. TSP has been demonstrated to bind to integrins of the alpha v beta 3 and alpha IIb beta 3 class. The carboxy-terminal region of TSP also contains at least one binding epitope for a cell receptor. There are 2 well characterized genes for TSP and truncated forms of TSP have been detected which have inhibitory effects on angiogenesis. Finally, TSP can interact with fibrinogen and fibronectin, perhaps on cellular surfaces, which might serve as secondary receptor-like mechanisms for TSP binding and subsequent mediation of cell adhesion.
Cancer Metastasis Rev 1992 Nov
PMID:Thrombospondin as a mediator of cancer cell adhesion in metastasis. 138 98

The movement of lymphocytes through extracellular matrix (ECM) is an essential component of normal traffic and infiltration into inflammatory sites. This review surveys current knowledge of the mechanisms of lymphocyte migration through ECM, most of which was derived from work with in vitro models of basement membranes, interstitial stroma, or their constituent components. Normal lymphocyte motility is an extremely plastic property. Naive lymphocytes tend to be unresponsive to ECM components and many chemoattractants, but when exposed to antigens, artificial mitogens and certain lymphokines, they rapidly acquire locomotory capacity, which is expressed as increased polarity, adhesiveness, invasiveness and chemotactic response. Acquisition of locomotory capacity is associated with the G0/G1 transition, and activation of protein kinase C appears to be a key event. Preliminary evidence indicates that mitogenesis and differentiation to the memory phenotype trigger a long-lasting, possibly permanent elevation of locomotory response to ECM. Receptors for fibronectin, laminin and collagens I and IV have been implicated as mediators of lymphocyte motility, but these receptors have not been characterized in detail. Heparanases facilitate T cell movement through the basement membrane, but the role of proteases has not yet been defined. Major gaps remain in our understanding of the connection between in vitro models and specific stages of the infiltration process in vivo and of motility regulation at the molecular level.
Invasion Metastasis 1992
PMID:Lymphocyte migration through extracellular matrix. 139 3


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