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

Tumor invasion and metastasis involves the interaction between tumor cells and basement membrane, which is mediated in part by laminin receptors/laminin-binding proteins. We have reported that a 32-kDa laminin-binding protein (LBP-32) was overexpressed in colorectal cancer at the messenger RNA (mRNA) level and correlated with clinical staging. However, the function of this protein is not yet defined. In this study, we have analyzed the role of LBP-32 in tumor cell attachment and invasion through various basement membrane components. Blockade of LBP-32 synthesis with an anti-sense RNA was utilized in this study. The partial sequence (237 bp) of LBP-32 was inserted into the EMSV33 vector in the sense or antisense direction. Clone A, a poorly differentiated human colon carcinoma cell line, was transfected with EMSV33 alone (control), or EMSV33 with the insert in sense (LBP-S) or anti-sense (LBP-AS) direction using lipofectin. The cell adhesion assays (at 37 degrees C for 75 min) were performed using parental Clone A cells or the transfectants. Specific attachment to wells coated with laminin, fibronectin, or type IV collagen was evaluated. In vitro cell invasion assays were performed using the parental clone A cells and their transfectants to assess the passage through polycarbonate filters coated with matrigel, a reconstituted basement membrane. The results showed that (a) laminin and collagen IV (but not fibronectin) play a role in colon cancer cell attachment to substrata, and (b) anti-sense RNA of LBP-32 inhibits tumor cell attachment and invasiveness in vitro. These findings suggest a role for LBP-32 in colon cancer progression and metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-sense RNA of 32-kDa laminin-binding protein inhibits attachment and invasion of a human colon carcinoma cell line. 153 86

Cultured human neuroblastoma cells can be classified morphologically into 3 types: neuroblastic (N), intermediate (I) and substrate adherent (S). Neuroblastoma cells of all types were found to attach and display distinct morphological characteristics on fibronectin, with S-type cells attaching better than N-type cells. Studies of the expression of integrin fibronectin receptors (alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1 and alpha V beta 1) were carried out using a total of 26 morphologically distinct cell lines and their subpopulations. Fluorescence-activated cell sorting (FACS) analysis and immunoprecipitation revealed that all S-type cells expressed abundant alpha 5 beta 1, while N-type cells barely expressed this molecule. Although alpha 3 beta 1 expression of S-type cells was also higher than that of N-type cells, some N-type cells had significantly increased levels of this molecule. alpha 4 beta 1 was found to be randomly expressed. All cell lines tested expressed alpha V beta 1. Human neuroblastoma cells, the majority of which are N-type cells with very low alpha 5 beta 1 expression, are also contrasted with other childhood cancer cells (rhabdomyosarcoma, Ewing's sarcoma, and glioma), all of which expressed high levels of alpha 5 beta 1. The characteristic expression of integrin fibronectin receptors may account for the clinically unique tumor behavior, and the immunohistochemical staining for integrins may become a useful alternative to conventional histology in differential diagnosis and a marker for prognosis in neuroblastoma.
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PMID:Unique expression of integrin fibronectin receptors in human neuroblastoma cell lines. 153 85

Human neural-crest-derived tumor cell lines, including three neuroblastomas, an astrocytoma, a glioblastoma, a rhabdomyosarcoma and a melanoma were screened for the expression of the integrin alpha 4 beta 1 (VLA-4). The neuroblastomas IMR-32 and SK-N-SH, the astrocytoma 131-INI, the glioblastoma Fogerty and the rhabdomyosarcoma TE-671 expressed alpha 4 beta 1 as determined by cytofluorometry and immunoprecipitation. Another neuroblastoma line, LA-N-1, did not express alpha 4 beta 1. Analysis of immunoprecipitated alpha 4 beta 1 showed that the alpha 4 subunit from the various cell types differed in relative molecular weight (M(r)). The variability in the observed M(r) could be accounted for by differences in the levels of N-linked glycosylation. The observed variability in M(r) did not appear to affect function since intact cells and solubilized alpha 4 beta 1 bound to a synthetic peptide identical in sequence to the CS-1 region of the alternatively spliced IIICS domain of fibronectin, a known alpha 4 beta 1 ligand.
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PMID:Expression and ligand-binding function of the integrin alpha 4 beta 1 (VLA-4) on neural-crest-derived tumor cell lines. 153 75

Cell/fibronectin adhesion in extracellular matrices is partly mediated by integrin receptor recognition of RGD domains in fibronectin. Since blood contains significant levels of soluble fibronectin we have now investigated the occurrence of extracellular RGD-binding proteins. Attachment assays indicate that extracellular RGD-binding proteins prevent cell adhesion, suggesting their potential as novel secreted modulators of blood-borne cell adhesive interactions. These extracellular RGD-binding proteins also showed electrophoretic changes with reducing agents, suggestive of intrachain disulphide bonds, like those found in RGD-binding integrins. However, they differed from the latter in their electrophoretic profile, which was greatly dependent on the presence of protease inhibitors. Plasma from tumor-bearing mice showed a greater proportion of fast-migrating RGD-binding species under reducing condition compared to similarly treated normal plasma, suggesting that tumor development is associated with a partial degradation of extracellular RGD-binding proteins.
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PMID:Extracellular RGD-binding proteins modulate cell adhesion. 155 May 62

This study examined the role of fibronectin in promoting particulate attachment to sites of urothelial injury. Variables influencing adherence of the rat transitional carcinoma cell line 4909 and "non-cellular" styrene-divinylbenzene microspheres to fibronectin were studied in an in vitro system. A soluble synthetic peptide fragment (Gly-Arg-Gly-Asp-Ser [GRGDS]) duplicating the receptor binding domain of fibronectin (RGD) was used to determine whether cell adherence could be inhibited by fibronectin receptor blockade. In vitro findings were correlated with an in vivo assay of both cellular and non-cellular particulate adherence to injured urothelium. Time, plated cell density, substrate concentration, GRGDS concentration, and cell viability, were all found to be significant independent variables influencing in vitro cellular adherence (p less than 0.0001). Receptor blockade with GRGDS significantly decreased in vitro tumor cell adherence to fibronectin. In vitro microsphere binding increased as a direct function of fibronectin concentration but was not time dependent (p less than 0.0001 and p = 0.14 for fibronectin concentration and time respectively). The in vivo adherence of both tumor cells and microspheres was significantly increased in injured bladders compared to controls (p less than 0.01). Receptor blockade with GRGDS failed to inhibit in vivo cell adherence to sites of urothelial injury. Microspheres proved to be competitive inhibitors of cellular adherence in competitive binding assays. In vitro microsphere binding demonstrated a pH dependence with maximal binding at pH 7.2. These data suggest that in vitro tumor cell adherence to fibronectin differs from in vivo tumor cell adherence to sites of urothelial injury. Manipulations which inhibit in vitro adherence, specifically fibronectin receptor blockade and cell death, fail to effect in vivo binding to the extreme that non-cellular particulate appears to bind to the same site, and with similar affinity, as cellular particles.
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PMID:In vitro particulate adherence to fibronectin: correlation with in vivo particulate adherence to sites of bladder injury. 156 98

Since Coman in 1944 observed that decreased adhesiveness is a characteristic of malignant cells and Grobstein 10 years later demonstrated that epithelial and mesenchymal cells influence each other when separated by a cell-impermeable filter, components of the extracellular matrix have been suspected of playing an active role in cancer growth. Breast cancer is frequently characterized by an increase in connective tissue fibroblastic cells and extracellular matrix, the nature and molecular composition of which is gradually being revealed. Two of the most studied and hence best known components of extracellular matrix are fibronectin and laminin. They are called adhesive or structural glycoproteins, because they are part of the stabilizing scaffold, which links connective tissue cells to each other (fibronectin) and connects connective tissues with parenchymatous cells via basement membranes (laminin). Both molecules harbour a variety of specific binding sites, which allow them to participate actively in basic dynamic processes such as cell modulation, -attachment, -spreading and -migration. Tetranectin is a recently discovered protein of human plasma and nucleated cells, which is suspected of participating in tissue degradation and proteolysis through its specific binding to plasminogen, a member of the plasminogen activation system. The immunohistochemical studies of fibronectin, laminin and tetranectin, on which this thesis is based, were undertaken in order to investigate if qualitative or quantitative changes of these proteins between benign and malignant breast tissue would reflect the net effect of the different inherent characteristics of breast cancer cells known from experimental studies (i.e. unanchored growth, proteolysis, metastatic spread and de novo production of extracellular matrix components). A significant increase in stromal fibronectin was a consistent finding in all infiltrating carcinomas, permitting the discrimination between such tumors and benign proliferative lesions as well as between carcinomas with a sarcomatoid appearance and true breast carcinomas. However, as a possible consequence of tumor heterogeneity this stromal reactivity pattern varied and tended to disappear focally along the invasive front of tumors with a high metastatic potential. A concurrent increase in the tumor cell expression of FN was found in poorly differentiated tumors, which could either be due to increased fibronectin production by the more anaplastic tumor cells or internalization of exogenous fibronectin bound to its receptor. Whereas most of the extracellular fibronectin in breast cancer is thought to be produced by the stromal fibroblasts, extracellular laminin is considered a product of the epithelial tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The distribution of fibronectin, laminin and tetranectin in human breast cancer with special attention to the extracellular matrix. 157 6

Matrix-bound fibronectin (FN) appears to be involved in cell adhesion and motility mediated by integrin receptors. Although lymphoid cells and other cell types are capable of producing and secreting FN, the precise role of this secreted FN-like factor in regulating immune reactions is unclear. In the present study we analyzed the adhesive properties of FN secreted by rat CD4+ T cells and clone cells activated by the T cell mitogen concanavalin A (Con A), antigen, or via the CD2 pathways, or by macrophages (M phi) activated by lipopolysaccharide (LPS). Immobilized culture supernatant (CS) from the activated T cells or M phi supports the adhesion of activated rat or human CD4+ T cell or murine tumor cell. These CS contained FN and were more potent at facilitating cell adhesion then plasma FN. The adhesion activity of CS was attributed to FN because (a) gelatin columns depleted the FN present in the CS and (b) pretreating the cells with peptides of the cell-binding domain of FN abrogated their ability to bind CS. CS-mediated adhesion appears to occur primarily via the recognition of the Arg-Gly-Asp (RGD) by the beta 1-integrin-specific receptors of the adhesive cells. Thus, we postulate that FN secreted by various types of leukocytes is involved in promoting essential cell-matrix interactions, possibly affecting cell-adhesive and migratory processes at inflammatory or extravasation sites.
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PMID:Activated T lymphocytes and macrophages secrete fibronectin which strongly supports cell adhesion. 157 55

Myofibroblasts from human breast carcinomas were identified and experimentally generated in culture, and a possible function was examined. The frequency of alpha-smooth muscle actin immunoreactive cells was evaluated as a measure of myofibroblast differentiation in primary culture. Few or no alpha-smooth muscle actin-positive stromal cells (6.1 +/- 8.4%) were identified in primary cultures from normal breast tissue (n = 9). In contrast, high frequencies (68.8 +/- 15.1%) were observed in primary cultures from carcinomas (n = 19). The frequencies of myofibroblasts in primary cultures were almost identical to those obtained in the corresponding cryostat sections (69.1 vs. 68.8%). A possible precursor cell to the myofibroblast was looked for among typical fibroblasts and vascular smooth muscle cells. Purified blood vessels containing both fibroblasts and vascular smooth muscle cells were embedded in collagen gel and incubated with medium conditioned by breast epithelial cells. Fibroblasts rather than smooth muscle cells were recruited from the blood vessels. In medium conditioned by carcinoma cell lines or in co-cultures of carcinoma cell lines and purified fibroblasts, alpha-smooth muscle actin and the typical myofibroblast phenotype were induced in otherwise alpha-smooth muscle actin-negative fibroblasts. The effect of myofibroblasts on cellular movement--essential to neoplastic cells--was analyzed. Spontaneous motility of tumor cells (MCF-7) was entirely suppressed in a collagen gel assay. Under these conditions tumor cell motility was selectively mediated by direct cell-to-cell interaction between tumor cells and myofibroblasts. Under chemically defined conditions, interaction was dependent on the presence of plasminogen. Anti-plasminogen, soybean trypsin inhibitor, and anti-fibronectin partly neutralized the effect of plasminogen. It is concluded that elements of myofibroblast differentiation and function may be studied in culture.
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PMID:Identification, paracrine generation, and possible function of human breast carcinoma myofibroblasts in culture. 158 5

VLA-1 to VLA-6 are cell-surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin. In addition, VLA-4 binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion prerogative for lymphocyte extravasation or 'homing'. Using frozen tissue of normal lymphoid organs and of 100 morphologically and immunologically typed B cell neoplasias, monoclonal antibodies to all six VAL-alpha and to the common beta-chain were applied to serial sections. VLAs were found differentially expressed in cytologically and microtopographically defined B-cell subsets [follicular mantle zone cells (MZ), follicular center cells (FC), extrafollicular cells (EF), and plasma cells (PC)] of normal spleen, lymph node, and thymic medulla (which contains an EF compartment). Thus, these cell types, which correspond to discrete stages of B cell development, can also be defined by their VLA status. Acute B lymphoblastic leukemia (ALL) was VLA-1-, 2-, 3 +/-, 4 +/-, 5 +/-, 6-. The VLA-1-, -2 +/-, 3+, -4+, -5+, -6-phenotype of chronic B lymphocytic leukemia (CLL) resembled that of MZ. Hairy cell leukemia (HCL) differed from CLL in its tendency to lack VLA-2, in its consistent lack of VLA-3, and altogether resembled splenic EF in its VLA profile. Mantle zone lymphoma (MZL) consistently expressed VLA-3 and -4 and frequently VLA-5. Nodal follicular center cell lymphomas (FCCL) were VLA-1- and -2- and very rarely expressed VLA-5 and -6. Thus, FCCL although roughly corresponding to FC, tended to aberrantly express VLA-3 and/or VLA-4. Burkitt's lymphoma resembled FCCL but expressed VLA-4 more frequently and at higher levels. Mediastinal clear cell lymphoma of B-cell type differed from FCCL in its regular lack of VLA-3, -5, and -6 and in frequently lacking VLA-4. Medullary plasmacytoma was VLA-1-, -2-, -3 +/-, -4 +/-, -5-, -6+, thus being the only B cell neoplasia which was consistently VLA-6+. With respect to the well-known clinical characteristics of the B cell malignancies examined, the leukemic phenotype might crucially depend on the presence of VLA-5.
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PMID:Adhesion molecules VLA-1 to VLA-6 define discrete stages of peripheral B lymphocyte development and characterize different types of B cell neoplasia. 158 89

We investigated the effects of nonlethal gamma radiation on the metastatic potential of the murine tumor cell line, B16 melanoma. The ability of B16 cells to adhere to fibronectin, which is in part mediated by the alpha IIb beta 3 integrin receptor, is predictive of metastatic potential. We determined that exposure to 0.25-2.5 Gy gamma radiation significantly enhanced B16 cell adhesion to fibronectin. The radiation-enhanced adhesion was dependent on enhanced expression of the alpha IIb beta 3 integrin. We observed that 15 min after 0.5 Gy radiation, 99% of irradiated B16 tumor cells were positively labeled with monoclonal antibodies directed against alpha IIb beta 3 compared to 22% of sham-irradiated cells. Radiation-enhanced expression of the alpha IIb beta 3 receptor is reversible and down-regulation begins within 2-4 h postirradiation. Finally, we found that irradiation significantly enhanced the ability of B16 cells to form metastases in a lung colony assay. It is concluded that a relationship exists between radiation effects on the B16 tumor cells, alpha IIb beta 3 receptor expression, adhesion in vitro, and metastasis in vivo. We suggest that low-dose radiation, at levels comparable to those used in fractionated or hyperfractionated radiotherapy, may alter the metastatic phenotype and potential of surviving tumor cells via a rapid alteration in their surface expression of alpha IIb beta 3 integrin receptors.
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PMID:Radiation-induced increase in expression of the alpha IIb beta 3 integrin in melanoma cells: effects on metastatic potential. 159 53


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