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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since tumor progression is dependent on the ability of malignant cells to interact with the extracellular matrix, molecules on the cell surface which mediate cell-substratum interactions are likely to be important regulators of tumor invasion and metastasis. The purpose of this study was to examine the distribution of one such group of cell adhesion receptors, the integrins, in benign and malignant lesions of human melanocytes. The distribution of integrin adhesion receptors was defined on cells in culture derived from normal and malignant melanocytes and in tissue sections from benign to increasingly malignant melanocytic lesions using a panel of monoclonal antibodies against specific integrin subunits. Cells in culture expressed a large variety of integrins, including all of the previously characterized members of the beta 1 subfamily plus the alpha v/beta 3 vitronectin receptor. The expression of integrins was similar in cells cultured from either benign or malignant lesions. In contrast, consistent differences were noted in integrin expression by cells within tissues containing metastatic and vertical growth phase melanomas when compared to radial growth phase melanoma cells and cells within nevi. Most notably, the expression of the beta 3 subunit was restricted exclusively to cells within vertical growth phase and metastatic melanomas. The presence of this integrin may be important in the development of tumor invasiveness and could be useful as a marker of melanoma cells entering the more aggressive phase of the malignant process.
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PMID:Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. 220 39

It has been assumed that S-protein (vitronectin) associates with terminal C5b-9 complement complexes only when the latter fail to attach to target lipid bilayers, thereby forming inactive fluid-phase SC5b-9 complexes. Using monoclonal anti-S-protein antibodies, we show here that a minor portion of C5b-9 complexes associated with both homologous and heterologous cells contain S-protein. This conclusion derives from Western blot analyses, from the sedimentation behaviour of solubilized S-protein, and from the fact that the protein co-immunoprecipitates with C5b-9(m). Association of S-protein with C5b-9(m) takes place primarily at the stage of C9-binding. An average of less than or equal to 0.4 moles of S-protein are estimated to be present per mole C5b-9(m). Hence, only a fraction of C5b-9 complexes contain S-protein. The function of cell-bound S-protein is unknown. Haemolytic titrations with purified components failed to demonstrate any protective effect of S-protein on the lysis of sheep or human erythrocytes by C5b-9. S-protein bound to complement-lysed homologous or heterologous cells is readily detectable by conventional immunocytochemical staining. We conclude that differentiation between tissue-deposited fluid-phase C5b-9 and membrane C5b-9 complexes cannot be made on the basis of immunohistological stainings for S-protein alone.
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PMID:Complement S-protein (vitronectin) is associated with cytolytic membrane-bound C5b-9 complexes. 246 93

The arrays of proteins adsorbed from plasma onto a series of polystyrene copolymeric latexes were analyzed by enzyme-linked immunosorbent assay (ELISA) of washed beads and immunoblotting of proteins desorbed from the beads and separated by polyacrylamide gel electrophoresis (PAGE). Beads were prepared by continuous emulsion polymerization in the absence of surfactant. Coomassie brilliant blue staining of gel electropherograms of desorbed proteins indicated that the presence of small amounts of comonomers (1 to 10 mole %) significantly influenced the composition of the adsorbed protein layer. Immunoblotting revealed that fibrinogen, fibronectin, and vitronectin were adsorbed by all surfaces investigated. C3 and Clq adsorption varied significantly with copolymer composition. The ELISAs revealed that although the concentrations of vitronectin and fibronectin in plasma are similar, the extent of vitronectin adsorption from 70% to 85% plasma was greater by two orders of magnitude than fibronectin adsorption. Vitronectin adsorbed on carboxylic acid-containing copolymers reacted more strongly with a conformationally sensitive antivitronectin monoclonal antibody (MoAb) than vitronectin adsorbed to polystyrene and was more susceptible to cleavage by plasma proteases(s). The results show that vitronectin is a major protein adsorbed from concentrated plasma and that small changes in the chemical composition of a copolymer profoundly affects the extent and nature of protein adsorption from complex mixtures such as plasma.
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PMID:Identification of vitronectin as a major plasma protein adsorbed on polymer surfaces of different copolymer composition. 247 28

Identification of antigens by monoclonal antibodies (MAbs) on sections of human melanoma by immunoperoxidase techniques was used to determine whether certain adhesion molecules and "selectin-like" molecules may be related to the metastatic potential of primary melanoma. The adhesion molecules examined were the leukocyte function antigen (LFA-1) and its ligand--intercellular adhesion molecule-1 (ICAM-1), the receptor alpha V beta 3 for vitronectin, its subunits alpha V and beta 3, and the CD36 receptor for thrombospondin (TSP). The criteria used to establish metastatic potential were relation of the molecules to tumor thickness and differences in expression: (i) between radial and vertical growth phases of the primary tumors and (ii) between 34 primary and 21 unrelated metastases. By these criteria ICAM-1, alpha V beta 3 and its subunit were associated with the malignant potential of primary melanoma. These molecules were not expressed on nevi or other skin cancers with low metastatic potential such as squamous (SCC) and basal cell carcinomas (BCC). In contrast, expression of TSP and the CD36 receptor for TSP were not related to metastatic potential. CD36 was expressed widely not only on melanoma but also on BCC, SCC and nevi. Similarly, the selectin-like molecule, CD44, was widely expressed on melanoma and non-melanoma carcinomas. The lymph node homing receptor, Leu 8, and the cutaneous lymphocyte antigen (CLA) were not detected on melanoma. Leu 8 was present on normal epithelium and SCCs, and common leucocyte antigen (CLA) was detected on lymphocytes in the epithelium and near melanoma. These results support previous suggestions that expression of ICAM-1 and V beta 3 integrin or its subunit beta 3 on melanoma may be a useful prognostic marker in primary melanoma. They do not support a role for CD44, Leu 8, CLA and TSP or its receptor CD36 in the metastatic process in melanoma.
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PMID:Immunohistological examination of the relationship between metastatic potential and expression of adhesion molecules and 'selectins' on melanoma cells. 751 76

The interaction of thrombin with plasminogen activator inhibitor 1 (PAI-1) is shown to result in the simultaneous formation of both cleaved PAI-1 and a sodium dodecyl sulfate-stable thrombin-PAI-1 complex. The kinetics of this reaction can be described by a "suicide substrate" mechanism that includes a branched reaction pathway, which terminates in either the stable inhibitor-enzyme complex or the cleaved inhibitor plus free enzyme. Because of the branched pathway, approximately three moles of PAI-1 are needed to completely inhibit one mole of thrombin. Heparin and vitronectin enhance the rate of inhibition from 9.8 x 10(2) L mol(-1) s(-1) to 6.2 x 10(4) L mol(-1) s(-1) and 2.1 x 10(5) L mol(-1) s(-1), respectively, under optimal conditions. In addition to enhancing the rate of inhibition, both cofactors increase the apparent stoichiometry of the PAI-1-thrombin interaction, with cofactor concentration dependencies similar to the inhibition reaction. Thus, at 37 degrees C approximately six cleavage reactions occur per inhibition reaction. Therefore, thrombin will efficiently inactivate PAI-1 in the presence of either vitronectin or heparin, unless a sufficient excess of the inhibitor is present. These results show that physiological cofactors are able to switch a protease-serpin inhibition reaction to a substrate reaction, depending on the local concentrations of each of the components.
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PMID:The suicide substrate reaction between plasminogen activator inhibitor 1 and thrombin is regulated by the cofactors vitronectin and heparin. 929 20

The expression of the beta3 integrin subunit was investigated in 130 fixed, paraffin-embedded specimens of human melanomas and nevi using two different monoclonal antibodies. Expression was not observed in melanocytes and was absent or low in most nevi. In primary melanomas, expression was absent or low in the nontumorigenic radial growth phase, which includes the classes of in situ and microinvasive melanomas. In contrast, expression was high in the tumorigenic or vertical growth phase compartment of many primary melanomas and in most metastatic melanomas. Expression patterns were similar with the two antibodies, SSA6 and SAP, and was membrane-related as well as cytoplasmically expressed. In those nevi that reacted focally, the reactivity tended to occur in the dermal component of neurotized nevi, and in Spitz nevi, where the reactivity was stronger and more diffuse. A few dysplastic nevi showed focal reactivity of the junctional component. These results are consistent with tumor progression-related expression of the beta3 integrin, which is expressed in melanocytic tumors as the alphavbeta3 integrin, having affinity for matrix molecules, including vitronectin and fibronectin. In all melanomas, and in the subset of tumorigenic vertical growth phase melanomas, expression increased with thickness (P < .01). For this reason, and because ligation of this integrin has been shown in vitro to have several properties that may be related to the malignant phenotype, it is likely that expression of this marker may have prognostic value. However, because of its consistent and strong expression in Spitz nevi, the diagnostic utility of this marker will likely be limited.
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PMID:Progression-related expression of beta3 integrin in melanomas and nevi. 1033 28

Emergence of the invasive phenotype is a key event in the progression of human melanoma from benign proliferative lesions to malignant lesions. Recently we successfully selected in vivo from a poorly metastatic M4Beu. human melanoma cell line two variants (7GP and T1P26) that generate a higher frequency of spontaneous metastases to the lungs into immune-suppressed neonatal rats. Both cell lines showed no significant differences in the integrin profile of the subunits analyzed except for beta3, which was reduced to a background level in metastatic variants. To investigate how these variant sublines of human melanomas manage to sustain growth in the absence of alpha(v)beta3, a subtractive immunization approach was used to elicit host antibody response against cell surface proteins expressed on metastatic variants. In this study, a new monoclonal antibody (MoAb), LY1, that is highly specific for the 7GP and T1P26 variants, was isolated. LY1 identifies a membrane protein of Mr 55,000 on melanoma variants with epitopes that were resistant to sugar-cleaving enzymes. Immunostaining cells from variants by LY1 showed that staining is distributed to the cell periphery with high labeling intensity at the cell-to-cell contact points. This MoAb significantly inhibited invasion of metastatic variants through a reconstituted basement membrane (Matrigel) in vitro. Moreover, tumor growth of melanoma variants was dramatically affected in vivo with this MoAb. In vitro studies indicate that the LY1 MoAb does not inhibit chemotactic migration of the metastatic variants, the adhesion of tumor cells to vitronectin, collagen IV, fibronectin, and laminin, or cell proliferation. Expression of this antigen is high in human striated muscle, heart, spleen, brain, and lung and absent in kidney, liver, and pancreas. Using 59 fixed, paraffin-embedded archival tissues of human melanomas and nevi, LY1-reactive cells were not observed in melanocytes, nevi, or radial growth phase primary melanomas. In sharp contrast, LY1 selectively stained melanocytes derived from the vertical growth phase of many primary melanomas and metastatic melanomas. These results provide evidence that the Mr 55,000 protein expressed by selected variants with increased metastatic properties in vivo plays a functionally important role in determining metastasis. This molecule may represent a new metastatic risk marker in human melanoma and may be of biological importance in the identification of fatal metastatic subpopulations that have acquired competence for metastasis production.
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PMID:A new Mr 55,000 surface protein implicated in melanoma progression: association with a metastatic phenotype. 1105 82

Therapeutic strategies based on cell and tissue engineering can be advanced by developing material substrates that effectively interrogate the biological compartment, with or without the complimentary local release of growth factors. Poly(ether ester) segmented copolymers were engineered as model material systems to elucidate the interfacial molecular events that govern the function of adhered cells. Surface chemistry was modulated by varying poly(ethylene glycol) (PEG) length and mole fraction with poly(butylene terephthalate) (PBT), leading to differential competitive protein adsorption of fibronectin and vitronectin from serum and consequently to different cell attachment modes. Adhesion within the hydrogel-like milieu of longer surface PEG was mediated via binding to the CD44 transmembrane receptor, rather than the RGD-integrin mechanism, whereas greater substrate-bound fibronectin resulted in cell adhesion via integrins. These adhesion modalities differentially impacted morphological cell phenotype (spread or spheroid) and the subsequent expression of mRNA transcripts (collagen types II, I) characteristic of phenotypically differentiated or dedifferentiated chondrocytes, respectively. These results demonstrate that materials can be designed to directly elicit the membrane bound receptor apparatus desired for downstream cellular response, without requiring exogenous biological growth factors to enable differentiated potential.
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PMID:Modulation of chondrocyte phenotype for tissue engineering by designing the biologic-polymer carrier interface. 1709 26