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

Fibronectin plays a major role in the adhesion of many cell types. The extent of cell adhesion in vitro is related not only to the ability of the cells to interact with matrix-bound fibronectin, when it is present, but also to the synthesis or lack of synthesis of fibronectin by the cells, and to the lack of deposition of synthesized fibronectin into an insoluble matrix surrounding the cells. Many malignant cells, regardless of whether they synthesize subnormal or normal amounts of fibronectin, fail to deposit that fibronectin into a surrounding insoluble matrix. The lack of fibronectin around such cells appears to reflect a general absence of extracellular matrix since other matrix components, such as collagen, laminin, and heparan sulfate proteoglycan, are concomitantly missing. Cells that lack their own cell surface fibronectin due either to lack of deposition or to lack of synthesis can nevertheless adhere to insoluble fibronectin matrices elaborated by other cells. These cellular characteristics appear to be associated with cell migration in vivo during embryogenesis, and the same characteristics may enhance the invasive potential of malignant cells. The remarkable effects that fibronectin has on cellular adhesion and the association of lack of extracellular matrix components with poorly differentiated and highly metastatic tumors in vivo mandates that more be learned about the molecular and cellular details of the interactions of cells with their surrounding matrix. Important information concerning tumor invasion will parallel such an understanding and may eventually become the basis for therapeutic approaches.
Cancer Metastasis Rev 1984
PMID:Fibronectin in cell adhesion and invasion. 632 88

In this review some of the major mechanistic pathways by which tumor cells are thought to invade host tissues are discussed. Tumor invasion has been conceived to be the result of pathological, close-range interactions between malignant cells and host stroma. The sequence of events that characterize invasion can be summarized as follows: (a) Tumor cell clusters break from the confinement of the primary tumor. Loss of intercellular junctions (desmosomes), alterations in the chemical composition and physical properties of the cell surface coat (loss of fibronectin and heparan sulfate; excessive amounts of hyaluronate), and loosening of cell-substrate interactions (loss of hemidesmosomes, fibronectin, and heparan sulfate), are among the most frequently listed causes of tumor cell shedding. (b) Increased proteolytic activities at the invasion front cause focal alterations in the surrounding extracellular matrix, thereby changing its physical properties. Collagenases and cathepsins, as well as elastase and other neutral proteinases are the enzymes most frequently associated with matrix destruction and invasion. In some tissues this process is effectively regulated by inhibitors of matrix-degrading, proteolytic enzymes. (c) Tumor cells migrate into the altered matrix, possibly moving as aggregates along guidance tracks provided by host structures (blood vessels, lymphatics, nerves) or matrix macromolecules (collagen and fibronectin tracks). Migration seems to be preceded by increased swelling of glycosaminoglycan (i.e., hyaluronate) in the matrix, ahead of the migrating cell population. Various host cell types (mast cells, fibroblasts, endothelial cells, macrophages, etc.) may participate in these events.
Cancer Metastasis Rev 1983
PMID:Tumor invasion and host extracellular matrix. 635 11

Since the discovery of fibronectin as a transformation-sensitive 'cell surface' protein, it has been the focus of intensive studies. Fibronectin has multiple interactions and functions and is composed of distinguishing properties of malignant cells, properties. Invasiveness and metastasis, distinguishing properties of malignant cells, involve penetration through components of the extracellular matrix. Enzymatic degradation of matrix components is involved in these phenomena. Proteolytic targets of the pericellular matrices of cells in culture include fibronectin that has been found to be even selectively susceptible to proteinases. Defined fragments of fibronectin have transformation-promoting activity in experimental conditions and such fragments, detected in tumor patient body fluids, may serve as markers for tumor progression.
Invasion Metastasis 1983
PMID:Fibronectin and its proteolytic fragments. Potential as cancer markers. 637 14

Using an immunoperoxidase procedure, we have examined the distribution of laminin and fibronectin in normal human large intestinal mucosa and in 50 cases of rectal adenocarcinoma for which extensive clinical follow up was available. In normal tissue, laminin staining was largely restricted to basement membranes, including that underlying the epithelial cells, whereas fibronectin was found in both basement membranes and surrounding connective tissue. In rectal carcinomas, basement membrane-like staining for laminin associated with tumour cells was found in only 27 out of the 50 cases studied. Statistical analysis showed that the presence of laminin-containing basement membranes was correlated with low histological grade (well-differentiated tumours), but not with stage (progression through the bowel wall and the development of lymph node metastases) and, in a highly significant way, with a reduced incidence of distant metastases and increased patient survival. Although fibronectin was found in tumour cell basement membranes where these were present, it was also found in the stroma of all 50 tumours. There was no apparent correlation between the presence of stromal fibronectin and grade, stage or development of metastases. Finally, attention is drawn to some of the technical difficulties in detecting basement membrane antigens in formalin-fixed tissue, the material most frequently available for retrospective study.
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PMID:Laminin and fibronectin in rectal adenocarcinoma: relationship to tumour grade, stage and metastasis. 637 37

Chemotherapeutic assays, using nitrosoureas, performed on tumor bearing rats have shown a regression of local tumor, accompanied with an amplification of pulmonary metastases, demonstrating that the treatment of metastasis differs from the treatment of a local tumor. Cells organizing a tumor are heterogeneous for their drug resistance, and for a series of properties including their ability to form metastasis. Metastatic cells have to leave the tumoral tissue, to traverse biological barriers, to resist to immune system, to implant and growth in the target tissue. An experimental model has been used to characterize metastatic cells. Metastatic potential has been defined as the ability to invade lungs. Highly metastatic cloned cell lines, such as subline 6, were strongly stimulated to proliferate by EGF, expressed fibronectin, actively degraded the extracellular matrix, rapidly attached to endothelial vascular cells, and resisted to natural killer lymphocytes. Inversely, weakly metastatic lines, such as subline 8, were preferentially stimulated by FGF and EDGF, poorly expressed fibronectin, did not degrade extracellular matrix, slowly attached to vascular cells, and were killed by NK lymphocytes. Studies on a large series of clones showed a diversity between them, and that no one property was determinant. Modulation of these characters by growth factors, hormones and immune state of the host is discussed, and leads to conclude that the expression of metastatic potential of a tumor depends on genetically defined characters and also on influences excerted by the host.
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PMID:[Experimental study of cancer metastasis]. 639 21

The spontaneous production of elongated derivatives by cuboidal rat mammary epithelial cells was examined with the use of a series of single-cell clones grown in tissue culture. Four representative cell lines derived from a 7,12-dimethylbenz[a]anthracene-induced mammary tumor in an inbred WF rat were examined for morphologic stability, chromosome number, presence of immunoreactive fibronectin, laminin, prekeratin, and milk fat globule membrane (MFGM) antigens, ultrastructural characteristics, and tumorigenicity in syngeneic hosts. Conversion of cuboidal to elongated cells occurred by way of apparent morphologic intermediates, examples of which were isolated and cloned. Levels of immunoreactive fibronectin and laminin were greater in the elongated than the cuboidal clones, whereas the converse was true of prekeratin. MFGM antigens were present to a variable extent in all 4 clones. When grown on 0.3% collagen gels, cells of Rama 37 CL-A3 and Rama 37CS-A2 cuboidal clones exhibited surface microvilli and desmosomes. A minority of elongated cells contained microfilamental structures and pinocytotic vesicles similar to those seen in myoepithelial cells; the remainder lacked distinguishing ultrastructural features. After injection into syngeneic recipients, Rama 37 CL-A3 cuboidal line gave rise to glandular tumors consisting of cuboidal cells arranged in acinar structures, Rama 37 E5 elongated line induced spindle cell tumors, and Rama 37 CS-A2 and Rama 37 E8 lines induced tumors containing nests of mixed spindle and cuboidal cells. The majority of these tumors failed to metastasize.
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PMID:Phenotypic instability of rat mammary tumor epithelial cells. 641 41

A series of cell lines was isolated from the metastasizing rat mammary tumor cell strain TMT-081. MS by single-cell cloning. Feeder cells were required for development of single tumor cells into clonal colonies. The rate, pattern, and incidence of metastases following injection of cells into the mammary fat pads of syngeneic rats were relatively similar for the various cell lines, with dissemination to the lungs and axillary and paraaortic lymph nodes. When a representative cell line termed Rama 800 was subcloned, one subline was nontumorigenic, and another gave a lower incidence of lung metastases, but the remainder had similar in vivo properties to the parental Rama 800 cells. The metastatic properties of Rama 800 cells were not affected by passage in vitro through 60 cell generations. No production of myoepithelial-like variants from Rama 800 cells was observed at the ultrastructural level. Antisera to keratin, actin, laminin, and fibronectin, which normally stain myoepithelial cells and basement membrane, failed to stain Rama 800 cells, either in cultures or in tumor sections. Heterogeneous staining of Rama 800 tumor cells with antiserum to epithelial cell-specific milk fat globule membrane antigens was seen in tumor sections but not in culture. Abundant microvilli and membrane blebs were observed on the surface of cultured Rama 800 cells, but no lumen formation, desmosomes, or tonofilaments were seen, either in vivo or in vitro. The results suggest that the metastatic epithelial-derived cell lines lack the ability to express features of myoepithelial cells, in contrast to cell lines isolated previously from nonmetastasizing rat mammary tumors.
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PMID:Lack of production of myoepithelial variants by cloned epithelial cell lines derived from the TMT-081 metastasizing rat mammary tumor. 648 88

Three cell lines, REM 134, 111 and 367, derived from canine mammary carcinomas have been used to induce tumours in athymic nude mice after subcutaneous injection. The histopathology of the tumours was compared and each was found to resemble closely the original tumour. This did not change after serial in vivo passage. Metastasis never occurred. Injection of REM 134 cells intracranially resulted in a fast-growing tumour which also did not metastasize; injection intrapleurally resulted in growths most commonly on the mediastinum with confinement to the chest cavity. Fibronectin was present in the subcutaneous tumours. Two of the cell lines were cloned in semi-solid agar. When tested, these clones induced tumours identical histologically to the uncloned ones. Finally, male and female mice were injected subcutaneously with the same number of cells from each of the three lines but the rate of tumour growth did not differ significantly between the two sexes.
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PMID:Studies of three canine mammary cell lines--II. In vivo properties. 654 15

The ability of retinoids to prevent or alter the course of experimental tumorigenesis is well established. We have extended these observations to include effects on establishment of tumors and tumor metastases. A diet containing excess retinyl acetate fed to rats prior to injection of a metastatic line of transplantable hepatoma, prevented establishment of secondary tumor foci while 75% of the animals fed adequate retinyl acetate showed pulmonary metastases. Metastatic ability may be related to the ability to bind fibronectins, proteins that link cells to an underlying stroma. Findings suggest involvement of higher gangliosides in the attachment of cells to a fibronectin-collagen complex. Prior to metastasis, hepatoma lines become depleted in the putative fibronectin receptor gangliosides as an end result of a complex cascade of altered glycosyltransferase activities. After metastasis, fibronectin receptors are apparently restored in those secondary tumor foci that become established. Analyses suggest that excess vitamin A may prevent the reappearance of fibronectin receptor gangliosides so that secondary tumor foci do not establish.
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PMID:Glycosylation reactions and tumor establishment: modulation by vitamin A. 694 82

We have examined cell clones obtained from a 13762 mammary adenocarcinoma tumor and its spontaneous lung metastasis for phenotypic stability during serial culture passage in vitro. Two clones that varied markedly in their metastatic properties were chosen for further examination. One of these clones (MTC) obtained from the parental transplanted tumor initially failed to metastasize within 23 days post-injection s.c. but gained the ability to form spontaneous pulmonary metastases after several serial passages in vitro. Another clone (MTLn3) derived from a spontaneous lung metastasis was initially higher metastatic from short-term culture, but lost the potential to form large numbers of spontaneous lung metastases with long-term culture. In contrast to MTA, clone MTLn3 displayed lymph-node metastasis, and the frequency of lymph-node involvement increased when late-passage cultures of MTLn3 cells were assayed in vivo. Both clones from late-passage cultures produced larger tumor sizes at the primary (mammary fat pad) injection sites compared to early passage cells. The morphologies of MTC cells changed with serial tissue culture passage, while the morphologies of MTLn3 cells did not change. The display of fibronectin on MTC cells by immunofluorescence did not change with culture passage; fibronectin was not detected in cultures of clone MTLn3. Fibronectin was also found on MTC cells by cell surface labelling using lactoperoxidase-catalyzed iodination-sodium dodecylsulfate polyacrylamide gel electrophoresis-autoradiography. Iodination of fibronectin on MTC cells did not vary with culture passage, and as in immunofluorescence experiments it was not detected on MTLn3 cells. There was a decrease in exposure of certain cell surface proteins on MTC cells with culture passage, but we did not detect modifications with this procedure that correlated with culture passage of MTLn3 cells. We conclude that prolonged culture in vitro can result in modifications fo metastatic and cell-surface properties of tumor cell clones.
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PMID:Phenotypic drift of metastatic and cell-surface properties of mammary adenocarcinoma cell clones during growth in vitro. 703 55


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