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

A series of polyomavirus-transformed rat cells with varying tumorigenic potential were tested for biophysical parameters possibly related to metastatic properties: adhesive capacity and strength of adhesion to different substrates (laminin, fibronectin and albumin), cell deformability and spreading. Two groups of cell lines were defined according to their higher or lower adhesive capacity. Adhesivity did not appear to be related to cell deformability and spreading. A weak correlation was suggested between low adhesivity and high metastatic potential. A selection method was devised to separate cell samples into 3 subpopulations with different adhesive strength. Two cell lines, originally different, were chosen for this study: Py-tsa A25 cells were less adherent and highly metastatic, and Py-WTA2 cells were more adherent and less metastatic. After s.c. inoculation into syngeneic Fisher rats, the 3 selected subpopulations of the 2 cell lines induced pulmonary nodules to varying degrees, but only the less adherent ones were able to induce visceral metastasis located in stomach and intestine. In this case, animal survival time was 30% lower than for the highly adherent selected cells. After 10 culture passages, the same subpopulations were able to metastasize only in the lungs. However, when the selection procedure was repeated, the less adherent cells were again able to yield visceral nodules. Tumorigenicity remained unchanged in all cases. Study of cell dissemination and arrest in vivo showed a rapid targeting of labelled tumor cells toward lungs and stomach 5 hr after intradermal injection, where they remained up to 72 hr. More adherent cells displayed delayed localization after injection (24 hr) and radioactivity decreased more rapidly.
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PMID:Relationship between cellular adhesiveness and metastatic activity in polyomavirus-transformed FR3T3 rat cell lines. 284 89

The interaction of tumour cells with basement membrane components is thought to be important in influencing their invasive and metastatic properties. This paper describes the effect of laminin on the attachment of radiolabelled glioma and B16 murine melanoma cells to tissue culture plastic and type IV collagen. With the exception of the non-metastatic B16 F1 variant, laminin (and fibronectin) stimulated cell attachment to tissue culture plastic. Although laminin stimulated the attachment of the B16 BL6 metastatic variant to type IV collagen, it consistently inhibited the attachment of the glioma cells under the same conditions. Laminin appeared to exert its effect by adsorption to the collagen and was not cytotoxic to the glioma cells. In contrast, fibronectin had very little effect on cell attachment to type IV collagen. One of the most unusual features of glioma is the rarity of metastasis to extraneural sites. However, the effect of laminin observed here may not be the only factor involved in the metastatic inefficiency of this tumour type.
Clin Exp Metastasis
PMID:Effects of laminin on the attachment of glioma cells to type IV collagen. 292 51

In 85 patients presenting with various cancers, changes in the frequencies of plasma fibronectin and of the carcino-embryonic antigen (CEA) were compared and the results were correlated with the degree of extension. Forty-six percent of patients with mammary adenocarcinoma had plasma fibronectin values higher than the age-related limit range, but only 18% had an increase in CEA. In patients with secondary metastases, the highest values were significantly different from those found in controls. In these cases, fibronectin was present in abnormal concentrations in more than 80% of the patients, and CEA in 50%. Positive fibronectin values were less frequent in other cancers, except those of the genital tract. Neither fibronectin nor CEA are organ-specific, yet these two tumoral markers differ in the frequency with which they appear, notably in patients with mammary carcinoma.
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PMID:[Blood fibronectin changes in various neoplasms]. 293 32

We have carried out enzymatic, immunofluorescence, and surface iodination studies which show that B16 melanoma cells express the single chain form of the urokinase type plasminogen activator (uPA) on their cell surface, and that these cells are capable of plasminogen-dependent fibronectin degradation. The significance of the expression of surface single-chain uPA and uPA activity to the metastatic process was examined by preincubating melanoma cells with uPA modulating agents followed by i.v. injection of the cells into mice and enumeration of pulmonary nodules 17 days later. B16 cells that had been pretreated with anti-uPA immunoglobulins that were inhibitory to uPA activity invariably showed significantly decreased numbers of metastases compared to controls. On the contrary, pretreatment with plasmin, which is not only the product of the uPA catalyzed reaction but is also able to convert single-chain uPA to uPA, significantly increased the numbers of metastases. Control treatments, which included normal rabbit and mouse immunoglobulins, monovalent noninhibitory anti-uPA Fab fragments, and various monoclonal and polyclonal antibodies directed against other B16 cell surface antigens, did not affect the metastatic potential of the cells. Divalent inhibitory anti-uPA F(ab)2 fragments, on the contrary, inhibited metastasis as efficiently as intact IgG. The results support the hypothesis that proteolysis of extracellular matrix components by cell surface-localized uPA may be a critical step during the process of tumor cell invasion and metastasis.
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PMID:Modulation of metastatic potential by cell surface urokinase of murine melanoma cells. 296 89

The distribution of fibronectin and laminin was examined by immunohistochemistry in 11 adenoid cystic breast carcinomas, six adenoid cystic carcinomas of mouth and salivary gland, and six cribriform ductal breast carcinomas. Both proteins were present lining cystic lumina and around tumour islands in all the adenoid cystic breast carcinomas and in five of six salivary gland tumours. Abundant laminin and fibronectin were dispersed among adenoid cystic tumour cells arranged in sheets. One adenoid cystic carcinoma from buccal mucosa showed a transition from a cribriform tumour positive for both fibronectin and laminin to a cribriform tumour negative for fibronectin and laminin to undifferentiated carcinoma. Fibronectin and laminin seemed to disappear simultaneously from tumour cell surfaces. Another adenoid cystic carcinoma from buccal mucosa was negative for fibronectin and laminin from the time of initial biopsy. This was the only tumour that gave rise to disseminated metastases, resulting in the death of the patient within two years of surgery. In cribriform invasive ductal breast carcinomas the linings of cystic lumina were always negative for fibronectin and laminin. Varying quantities were present at the tumour boundaries. We suggest that staining for fibronectin and laminin may be a valuable aid to the diagnosis of adenoid cystic carcinomas and that the absence of these proteins may have important prognostic implications.
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PMID:Laminin and fibronectin in adenoid cystic carcinoma. 300 73

Human liver specimens with primary hepatocellular and cholangiocellular carcinoma and liver metastases of cancers from different organs were studied for the distribution of fibronectin (Fn) by immunoperoxidase staining. With the exception of an undifferentiated type, all six well and moderately differentiated primary hepatocellular carcinomas contained Fn in the intercellular spaces and on the surface of certain cells of the tumour parenchyma, while in the case of three cholangiocarcinomas Fn could only be detected in the loose reactive connective tissue stroma. No Fn was observed around individual tumour cells in any of eleven carcinoma metastases in the liver. These findings indicate that hepatocellular but not cholangiocellular carcinomas synthesize Fn, while carcinoma metastases from other organs do not contain Fn in their parenchyma only in the reactive stroma. In this way the presence of Fn in the pericellular matrix of the tumour parenchyma may help to distinguish primary hepatomas from metastases. Metastases with strong fibroplastic character and pericellular fibrosis may, however, imitate Fn production.
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PMID:Fibronectin in differential diagnosis of primary hepatomas and carcinoma metastases in the liver. 301 68

The specificity and sensitivity of malignancy marker determinations in cerebrospinal fluid (CSF) are often insufficient. Even at the subclinical stage of the disease the marker should be present. The effect of therapy should be monitored and relapses noted. Thus high standards of methodology are required. There are many substances that may indicate a malignant process in the central nervous system. However, there are many pitfalls in their determination. Malignant cells may occur in CSF via processes involving leptomeningeal structures such as metastases and leukaemia, but primary brain tumours seldom show cells in CSF. Human chorionic gonadotrophin and alpha-fetoprotein determinations assist in the early detection of cerebral germ cell tumours and of relapses, even in the subclinical stage. Desmosterol may aid in the diagnosis of medulloblastomas and malignant gliomas and in monitoring therapy. Putrescine levels are elevated in CSF of patients with medulloblastoma and correlate with the clinical state, and serial analyses may reveal relapses. Fibronectin, when determined in CSF at the time of diagnosis, appears to be of great significance for the prognosis of acute lymphoblastic leukaemia. Ferritin and beta-2-microglobulin may help in some well-defined conditions. Brain-specific proteins and antibodies to them are non-specific markers whereas tumour-specific antigens and growth factors may be more significant.
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PMID:Malignancy markers in the cerebrospinal fluid. 305 81

The mechanism by which the murine fibrosarcoma clone PAK 17.15 induces platelet aggregation [tumor cell-induced platelet aggregation (TCIPA)] was studied because platelet activation by this clone is necessary for metastasis to the lungs. PAK 17.15 TCIPA was completely inhibited by ADP-clearing enzymes, such as apyrase, or a mixture of creatine phosphate and creatine phosphokinase. Thrombin and collagen were not involved in PAK 17.15 TCIPA. Further studies showed that ADP is most likely secreted from activated platelets and that membrane protein(s) on PAK 17.15 cells are responsible for platelet activation. Inasmuch as ADP-dependent platelet aggregation requires fibrinogen and can be inhibited by the Gly-Arg-Gly-Asp-Ser (GRGDS) synthetic peptide, the effect of this peptide on PAK 17.15 TCIPA was studied. PAK 17.15 TCIPA was completely inhibited by the GRGDS peptide (0.4 mM) but not by a control peptide, Gly-Arg-Gly-Glu-Ser (0.8 mM). In addition, the GRGDS peptide inhibited adhesion of PAK 17.15 cells to immobilized fibronectin. As expected, the GRGDS peptide almost completely inhibited lung colonization by iv injected PAK 17.15 cells in C57BL/6 mice. Our results indicate that GRGDS may inhibit pulmonary metastases by interfering with TCIPA as well as with tumor cell adhesion to extra-cellular matrix components in the host.
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PMID:Inhibition of tumor cell-induced platelet aggregation and experimental tumor metastasis by the synthetic Gly-Arg-Gly-Asp-Ser peptide. 318 95

Interactions of malignant or non-malignant human and rodent cells with the vascular wall were studied using perfused human umbilical cord veins. The integrity of perfused endothelium was confirmed by morphological and functional criteria. Highly malignant cells in vivo adhered to the endothelial cells, as shown by scanning electron microscopy. The specific attachment of radiolabelled malignant cells to the whole vein was already maximal within 30-60 min and remained stable for perfusion flow rates ranging between 10 and 60 ml/min. It increased proportionally to the number of cells infused and could be modulated by human platelets, human fibronectin and rabbit anti-laminin antibodies. In contrast, the binding of human or rodent non-malignant cells in vivo, of human red blood cells and of human platelets to the endothelial cells was negligible under similar experimental conditions. This perfusion system therefore represents a new model for elucidating some mechanisms involved in tumour cell arrest in vivo.
Invasion Metastasis 1988
PMID:Perfusion of human umbilical veins. A new approach to study the interactions of circulating malignant cells with vascular wall and their modulations. 322 47

Platelet-adhesive protein-tumor cell interaction was studied in vitro and in vivo. Monoclonal antibody 10E5, which inhibits binding of fibronectin and von Willebrand factor to the platelet membrane glycoprotein GPIIb-GPIIIa complex, inhibited the binding of mouse CT26 and human HCT8 colon carcinoma cells to platelets by 63-65%, whereas an irrelevant monoclonal antibody, 3B2, had no effect. Monoclonal antibody 6D1, which inhibits binding of von Willebrand factor to GPIb, also had no effect. RGDS, a tetrapeptide that represents the adhesive domain of fibronectin and von Willebrand factor inhibited binding of the tumors to platelets by 64-69%. Monospecific polyclonal antifibronectin antibody inhibited binding by 60-82%; anti-von Willebrand factor antibody inhibited binding by 75-81%. In vivo, polyclonal monospecific anti-mouse von Willebrand factor antibody inhibited pulmonary metastases induced by CT26 tumor cells by 53-64%, B16a amelanotic melanoma cells by 45% and T241 Lewis bladder cells by 46% without induction of thrombocytopenia. Pulmonary metastases with CT26 cells could be inhibited by induction of thrombocytopenia, and reconstituted by infusion of either murine or human platelets. Reconstitution of pulmonary metastases with human platelets could be inhibited 77% by preincubation of human platelets with monoclonal antibody 10E5 before infusion of platelets into mice. Thus, platelets appear to contribute to metastases by their adhesive interaction with tumor cells via the adhesive proteins fibronectin and von Willebrand factor.
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PMID:Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. 328 May 98


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