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PubMed1993

Extensive complement activation in hereditary porcine membranoproliferative glomerulonephritis type II (porcine dense deposit disease).

Massive glomerular deposits of C3 and the terminal C5b-9 complement complex (TCC), but no immune complex deposits were detected by immunofluorescence in porcine membranoproliferative glomerulonephritis type II. TCC deposits were always observed with concomitant deposits of vitronectin (S-protein) in membranoproliferative glomerulonephritis, in contrast to a piglet with mesangial glomerulopathy where TCC was present without vitronectin co-deposition. Enzyme immunoassays revealed extensive systemic complement activation in 1-week-old affected piglets, observed by low plasma C3 (about 5% of normal) and high plasma TCC (about 10 x normal). Affected piglets revealed some plasma complement activation already at birth, 3 to 4 weeks before recognizable clinical disease. It is concluded that porcine membranoproliferative glomerulonephritis represents a nonimmune complex-mediated glomerulonephritis caused by unrestricted systemic complement activation with C3 consumption, TCC formation, and glomerular trapping of complement activation products. A pathogenetic mechanism of a defective or missing complement regulation protein is suggested.

Animals↗
PubMedDate not supplied

Differential expression of extracellular matrix proteins and integrins in hepatocellular carcinoma and chronic liver disease.

UNLABELLED: Extracellular matrix (ECM) molecules play an important role in the orderly development, differentiation and function of tissues. The interaction of ECM with heterodimeric transmembrane glycoproteins called integrins is thought to be an important factor in cell-cell and cell-substrate adhesions in tumours, tumour invasion and metastases. PURPOSE: To investigate ECM and adhesion molecules in hepatocellular and breast carcinomas, chronic hepatitis and hepatic cirrhosis. MATERIALS AND METHODS: Frozen in liquid nitrogen and also paraffin-embedded biopsies from hepatocellular adenomas (3), well-differentiated (53) and poorly differentiated (19) hepatocellular carcinomas, lobular (3) and poorly differentiated (7) breast carcinomas, chronic hepatitis (10) and hepatic cirrhosis (10) were collected and investigated. Immunohistochemical techniques were applied for the detection of ECM molecules fibronectin, laminin, tenascin, vitronectin and integrins alpha 5 and beta 4. RESULTS: Poorer differentiation of the tumours was characterised by up-regulation of fibronectin, tenascin and vitronectin and downregulation of laminin and both integrins. These changes were observed in the interface between tumour and invaded tissues and within cancerous sinusoids. CONCLUSION: Increased expression of some ECM glycoproteins around tumour foci suggests a role in stimulating cancer cells or a host defence mechanism accompanied by desmoplastic response to them. Downregulation of laminin in poorly differentiated tumours identifying loss of basement membrane components and parallels quantitative changes in the expression of adhesion molecules in both hepatic and breast carcinomas. This may be an important step in enhancing local invasiveness of tumour cells, facilitating tumour spreading and biological malignancy.

Antibodies, Monoclonal↗
PubMed1993

Transforming growth factor-beta increases adhesion but not migration of bovine bronchial epithelial cells to matrix proteins.

We have evaluated the effect of transforming growth factor-beta (TGF-beta) on migration and adhesion characteristics of bovine bronchial epithelial cells. TGF-beta was a chemoattractant for bronchial epithelial cells; however, prior treatment of primary cultures of bovine bronchial epithelial cells with TGF-beta did not increase their migration when fibronectin, vitronectin, laminin, and type IV collagen were used as attractants in blind-well chamber migration assays. Similarly, treatment with TGF-beta reduced the sheet migration of bovine bronchial epithelial cells over matrix-coated dishes. However, treatment of bovine bronchial epithelial cells with TGF-beta did increase their attachment to matrix-coated dishes. Using antisera to integrins for fibronectin and vitronectin, flow cytometry analysis, and immunoprecipitation, we demonstrated that the expression of these receptors on bovine bronchial epithelial cells was enhanced by TGF-beta. Adhesion to a 60 kd tryptic fragment of fibronectin that is not involved in integrin-mediated cell binding was also increased by TGF-beta. Thus TGF-beta has important effects on bronchial epithelial cells that enhance the ability of these cells to adhere to matrix proteins but not to migrate to these same proteins.

Amino Acid Sequence↗
PubMed1993

Clusterin, the human apolipoprotein and complement inhibitor, binds to complement C7, C8 beta, and the b domain of C9.

Clusterin is a heterodimeric multifunctional protein expressed in a variety of tissues and cells. It forms high density lipid complexes in plasma and participates in the control of the lytic activity of the late complement complex (TCC, C5b-9). Together with vitronectin, clusterin binds to the nascent amphiphilic C5b-9 complex, rendering it water soluble and lytically inactive. To define the interactions that underlie the complement-inhibitory function of clusterin, we have examined the binding interactions between [125I]clusterin and the isolated components of the complex, C5b-6, C7, C8, and C9 and vitronectin. By using ligand blotting in the presence of Tween, specific binding of the labeled clusterin with C7, the beta-subunit of C8 and C9 was detected. Binding to C9 was competed by polymerized C9, but not by C8, C7, C6, and CD59, suggesting that the conformational change occurring during the hydrophilic-amphiphilic transition of C9 exposes the interaction site for clusterin. When thrombin-treated C9 was analyzed, clusterin was found to recognize the C9b fragment containing the hydrophobic membrane interaction segment. Both subunits of clusterin interact with C9 and are similarly potent in inhibiting C5b-9-mediated hemolysis and Zn+(+)-induced C9 polymerization. These results show that clusterin exerts its inhibitory effect by interacting with a structural motif common to C7, C8 alpha, and C9b.

Clusterin↗
PubMed1993

Characterization of the integrin specificities of disintegrins isolated from American pit viper venoms.

A new series of homologous disintegrins was isolated from the venoms of new world pit viper genus Bothrops, Crotalus, and Lachesis. The relative activities of each disintegrin in blocking adhesive protein binding activities of GPIIb-IIIa, alpha v beta 3, and alpha 5 beta 1 were determined and correlated with their primary amino acid sequences. Four disintegrins contained the RGDW sequence and were found to be approximately twice as effective in blocking the binding of fibrinogen to GPIIb-IIIa than inhibiting the binding of vitronectin to alpha v beta 3 in solid-phase ligand binding assays (IC50 = 7.3 and 17.2 nM, respectively). A second group of seven disintegrins contained the RGDNP sequence and were found to be more potent inhibitors of vitronectin binding to alpha v beta 3 than fibrinogen binding to GPIIb-IIIa (IC50 = 4.3 and 19 nM, respectively). The RGDNP containing disintegrins were also greater than 10-fold more potent than RGDW containing disintegrins in blocking the adhesion of cells mediated by alpha 5 beta 1. These data illustrate that amino acid sequences immediately adjacent to the RGD site of disintegrins can create an extended RGD locus which coupled with conformational display of the RGD sequence may be involved in determining integrin selectivity and affinity. This information has been used in separate studies to design conformationally constrained integrin antagonists with high affinity for platelet GPIIb-IIIa.

Amino Acid Sequence↗
PubMed1997

Molecular crosstalk between adhesion receptors and proteolytic cascades in vascular remodelling.

The multifunctionality of adhesion receptor ligands as well as the promiscuous nature of vascular integrins and nonintegrin-dependent adhesive interactions allow ligand-receptor binding of variable strength. The cooperation with pericellular proteolysis cascades is required for vascular remodelling during angiogenesis, atherogenesis or inflammatory processes. In particular, integrin-dependent cell contact, spreading and (trans-)migration can be modulated by ECM-associated PAI-1 and uPA-receptor driven reactions that are intimately linked to the invasive potential of cells. Recently, mechanisms of molecular crosstalk between these receptor systems have been recognized: (a) uPA-receptor may directly interact with beta 1- and beta 2-integrins on circulating blood cells; (b) av beta 3-integrin-directly binds to a matrix metalloproteinase; (c) uPA and PAI-1 balance the high affinity binding of vitronectin to uPA-receptor; (d) vitronectin-dependent cell adhesion and migration involving alpha v-integrins or uPA-receptor are blocked by active PAI-1 independent of its role as protease inhibitor. These results are compatible with vascular injury studies in uPA- and PAI-1 knock-out mice and provide new targets for the treatment of diseases associated with imbalanced vascular remodelling.

Animals↗
PubMed1997

Effect of PMA and IL-1 on matrix proteins with special reference to kidney mesangial cells.

Cytokines have different effects on the extracellular matrix proteins which were produced by a number of different cell lines. The extracellular matrix proteins fibronectin, collagen IV, vitronectin, laminin, proteoglycan, fetal proteoglycan and actin; and the cells human mesangial, BeWo, Hep G2 and BHK using APAAP and dot-blot assay were used. It was shown that IL-1 and PMA increased the staining intensity of proteoglycan, fibronectin and collagen IV and vitronectin and did not alter the intensity of staining. While PMA and IL-1 decreased but did not alter laminin, PMA increased the staining intensity of proteoglycan in mesangial cells but not altered in mesangial cells stimulated with IL-1. These results show that PMA and IL-1 altered the production and secretion of extracellular matrix proteins, these in turn could lead to the alteration of pore size, matrix properties and filtration of mesangial cells, and thus influence pathological conditions of renal diseases.

Cells, Cultured↗
PubMed1997

Expression pattern of extracellular matrix proteins in the pancreas of various domestic pig breeds, the Goettingen Minipig and the Wild Boar.

UNLABELLED: In spite of progress in biotechnology, isolation of porcine pancreatic islets remains a difficult task with unpredictable results. One reason could be the lack of knowledge as to the expression of extracellular matrix proteins in porcine exocrine and endocrine tissues, particularly in "islet capsules". Such proteins are subject to digestion by proteases, yet they might have a protective function for the fragile islets. OBJECTIVE: Of our study was a detailed histological analysis of the extracellular matrix proteins in various pig breeds. A broad panel of commercial, human-specific antibodies were used, since antibodies against porcine tissue were not available. METHODS: Frozen pancreatic tissue section of 7 domestic pig breeds, the Goettingen Minipig and the Wild Boar were stained with antibodies against collagen types I, II, III, IV, V, VI, VII, IX, laminin, fibronectin, vitronectin and elastin. Binding of antibodies was detected by immunoperoxidase and evaluated microscopically. Human and rat tissue was treated in the same way. RESULTS: (1) With the exception of anti-collagen type II, type VII and vitronectin, all antibodies revealed distinct binding patterns in the pancreas of the different pig breeds. However these antibodies bound on human cartilage and skin. (2) Collagen types I, III, IV, laminin and fibronectin are expressed on porcine pancreatic "islet capsules". (3) Expression levels of these proteins on "islet capsules" vary in the different pig breeds. However, no significant differences could be found in the expression pattern of collagen types I, III, IV, laminin and fibronectin, comparing domestic, experimental and wild type pigs. (4) Older individuals (Goettingen Minipig) appear to express higher levels of proteins on "islet capsules" than younger ones. CONCLUSIONS: Antibodies with specificity for human extracellular matrix proteins can be used successfully in the porcine pancreas. Thus, analysis of the structure and composition of porcine pancreatic tissue can be performed even without pig-specific antibodies. Particularly, the effects of various proteases and collagenases on the pancreatic tissue can now be monitored by immunohistochemical analysis allowing a rational design of protease mixtures for the isolation of pancreatic islets.

Animals↗
PubMed1999

Attachment of cultured human bone cells to novel polymers.

The initial attachment of human bone-derived cells (HBDC) to several polymer systems has been studied in vitro. A novel polymer system based on poly(ethyl methacrylate) polymer and tetrahydrofurfuryl methacrylate monomer (PEMA/THFMA) was compared with a variant in which THFMA was replaced by 2-hydroxyethyl methacrylate (PEMA/HEMA). Tissue culture polystyrene (TCPS) and polystyrene (PS) were used as reference materials. The ability of the substrates to adsorb the attachment glycoproteins fibronectin (Fn) and vitronectin (Vn) from serum and the subsequent effect on radiolabeled HBDC attachment were examined. Initial cell attachment from the medium containing 10% (v/v) serum was highest on TCPS; on PEMA/THFMA and PEMA/HEMA substrates it was about 25% of this level, and on PS it was only 10% of that on TCPS. Attachment of HBDC to all substrates was dependent on the presence of Vn, which, unlike Fn, was able to adsorb in the face of competition from other serum components. Both Vn and Fn were able to support cell attachment when precoated onto all substrates. In comparison to TCPS, PEMA/THFMA did not show enhanced adsorption of either Fn or Vn from serum, and this was reflected in the level of cell attachment. Interestingly, the potency of preadsorbed Fn for cell attachment was much higher on this substrate than on any other: 45 ng/cm2 Fn when adsorbed to PEMA/THFMA gave a level of cell attachment 1.6-fold higher than the same density of Fn on PS or TCPS. The maximum Fn surface density achieved on HEMA/PEMA was 16 ng/cm2. Cells on PEMA/THFMA showed typical clustering of the alpha5 beta1 Fn receptor, but this was not evident in cells attached to PEMA/HEMA even when precoated with Fn. This study indicates that the initial attachment of HBDC to all substrates was Vn dependent. It also indicates that on PEMA/THFMA the favorable presentation of subsequently adsorbed Fn may assist matrix assembly.

Biocompatible Materials↗
PubMed2001

Overexpression of homeobox gene HOXD3 induces coordinate expression of metastasis-related genes in human lung cancer cells.

Homeobox-containing genes are expressed in spatiotemporal fashion during embryogenesis and act as master transcription-regulating factors which control the expression of a variety of genes involved in morphogenesis. They are also expressed in a tissue-specific manner in normal adult tissues and appear to give cells spatial information in the maintenance of their architectural integrity. We transfected a HOXD3 class I homeobox-containing gene into human lung cancer A549 cells and investigated alterations in gene expressions and phenotypes related to the maintenance of tissue architecture in HOXD3-overexpressing A549 cells. In the HOXD3-overexpressing cell lines, expression of E-cadherin was lost and plakoglobin was strongly repressed, whereas integrin alpha3 and beta3 were up-regulated and N-cadherin and integrin alpha4 were newly expressed. Compared with parental and control transfectant lines, the HOXD3-overexpressing cell lines showed highly motile and invasive activity. Blocking experiments using anti-integrin beta1 and beta3 suggested that the increased haptotaxis of the HOXD3-overexpressing cells to vitronectin resulted from increased expression and activation of integrin alphavbeta3, and that overexpression of the HOXD3 gene converted the integrin beta1-dependent haptotaxis to fibronectin into both integrin beta1- and beta3-dependent one. HOXD3 overexpression increased production of matrix-degrative enzymes including matrix metalloproteinase-2 and urokinase-plasminogen activator. When the tumor cells were intravenously injected into the tail veins of nude mice, HOXD3 transfectants formed a significantly large number of metastatic foci in lungs compared with the control transfectants. These findings suggest that HOXD3 can act as a metastasis-promoting gene in human lung cancer A549 cells.

Antigens, CD↗
PubMed1995

Implication of the alpha v beta 3 integrin in the adhesion of the ovarian-adenocarcinoma cell line IGROV1.

Accumulating evidence suggests that integrins, which participate in many complex cellular processes, are important for tumor progression and metastasis. In order to understand the role of these cell-surface receptors and of their ligands in the biological behavior of ovarian tumor cells, we have examined the expression of integrins in the human ovarian-adenocarcinoma cell line IGROV1. These cells expressed the alpha v sub-unit and used it to attach on vitronectin (Vn). A monoclonal antibody (MAb) (69-6-5) specific to alpha v blocked the attachment of IGROV1 cells on Vn and fibrinogen (Fg), but not on fibronectin (FN) and other adhesive ligands. Immunoprecipitation of surface biotinylated cells followed by Western blotting showed that the alpha v sub-unit was associated with beta 3, but not with beta 1, beta 5 or beta 6. When cells were cultivated on glass coverslips or on Vn sub-stratum in serum-free medium, immunofluorescence staining with MAb 69-6-5 revealed the presence of alpha v at cell-cell contacts and at focal contacts, supporting its active participation in adhesion as part of a functional heterodimer. Furthermore, immunofluorescence data showed the presence of Vn as a fibrillar network in IGROV1 cells cultivated on FN-coated slides. These results suggest that alpha v beta 3 and its Vn ligand may play a important role in the behavior of ovarian epithelial tumors.

Adenocarcinoma↗
PubMed2001

Efficient accommodation of recombinant, foot-and-mouth disease virus RGD peptides to cell-surface integrins.

The engineering of either complete virus cell-binding proteins or derived ligand peptides generates promising nonviral vectors for cell targeting and gene therapy. In this work, we have explored the molecular interaction between a recombinant, integrin-binding foot-and-mouth disease virus RGD peptide displayed on the surface of a carrier protein and its receptors on the cell surface. By increasing the number of viral segments, cell binding to recombinant proteins was significantly improved. This fact resulted in a dramatic growth stimulation of virus-sensitive BHK(21) cells but not virus-resistant HeLa cells in protein-coated wells. Surprisingly, growth stimulation was not observed in vitronectin-coated plates, suggesting that integrins other than alpha(v)beta(3) could be involved in binding of the recombinant peptide, maybe as coreceptors. On the other hand, both free and cell-linked integrins did not modify the enzymatic activity of RGD-based enzymatic sensors that contrarily, were activated by the induced fit of anti-RGD antibodies. Those findings are discussed in the context of a proper mimicry of the unusually complex architecture of this cell-binding site as engineered in multifunctional proteins.

Amino Acid Sequence↗
PubMed2001

MT1-MMP initiates activation of pro-MMP-2 and integrin alphavbeta3 promotes maturation of MMP-2 in breast carcinoma cells.

We evaluated cellular mechanisms involved in the activation pathway of matrix prometalloproteinase-2 (pro-MMP-2), an enzyme implicated in the malignant progression of many tumor types. Membrane type-1 matrix metalloproteinase (MT1-MMP) cleaves the N-terminal prodomain of pro-MMP-2 thus generating the activation intermediate that then matures into the fully active enzyme of MMP-2. Our results provide evidence on how a collaboration between MT1-MMP and integrin alphavbeta3 promotes more efficient activation and specific, transient docking of the activation intermediate and, further, the mature, active enzyme of MMP-2 at discrete regions of cells. We show that coexpression of MT1-MMP and integrin alphavbeta3 in MCF7 breast carcinoma cells specifically enhances in trans autocatalytic maturation of MMP-2. The association of MMP-2's C-terminal hemopexin-like domain with those molecules of integrin alphavbeta3 which are proximal to MT1-MMP facilitates MMP-2 maturation. Vitronectin, a specific ligand of integrin alphavbeta3, competitively blocked the integrin-dependent maturation of MMP-2. Immunofluorescence and immunoprecipitation studies supported clustering of MT1-MMP and integrin alphavbeta3 at discrete regions of the cell surface. Evidently, the identified mechanisms appear to be instrumental to clustering active MMP-2 directly at the invadopodia and invasive front of alphavbeta3-expressing cells or in their close vicinity, thereby accelerating tumor cell locomotion.

Antibodies, Monoclonal↗
PubMed2004

Association of alphavbeta3 integrin expression with the metastatic potential and migratory and chemotactic ability of human osteosarcoma cells.

INTRODUCTION: Expression of adhesion molecules such as alphavbeta3 integrin has been associated with the metastatic potential of tumor cells. The purpose of this study was to determine whether alphavbeta3 expression correlated with the metastatic potential of human osteosarcoma cells. MATERIALS AND METHODS: We developed a series of sublines (LM2-LM7) from human osteosarcoma SAOS parental cells, with progressively increasing potential to form lung metastases in nude mice after intravenous injection. SAOS parental and LM2 cells were poorly metastatic, but LM7 cells resulted in visible metastatic lung nodules by 6-8 weeks. We quantified alphavbeta3 integrin expression using flow cytometry. RESULTS: alphavbeta3 expression correlated with the metastatic potential of the cells, with LM7 cells showing the highest expression. LM7 cell adhesion to vitronectin decreased after treatment with echistatin, a RGD-containing peptide antagonist of alphavbeta3. LM7 cells demonstrated higher chemotactic activity than SAOS cells to a homogenate made from lung tissue. This chemotactic activity was also inhibited by echistatin. These data indicated that alphavbeta3 was critical for the migration of LM7 cells to the lung homogenate. Chemotaxis to a liver homogenate was the same for LM7 and SAOS cells. Migration of LM7 cells through lung endothelial cells was higher than that through liver endothelial cells, and echistatin again inhibited this migration. CONCLUSIONS: alphavbeta3 integrin expression may play a role in the metastatic potential of osteosarcoma cells by enhancing the ability of the cells to migrate specifically to the lung. Alphavbeta3 integrin may therefore be a potential new target for osteosarcoma.

Animals↗
PubMed1991

Sandwich enzyme immunoassay for serum integrins using monoclonal antibodies.

We produced monoclonal antibodies (mABs) against human integrins. Competitive enzyme-linked immunosorbent assay (ELISA) revealed that each mAB bound to different antigenic determinants. We then developed sandwich-type enzyme immunoassays (EIAs) to measure the concentration of fibronectin receptor (FNR) and vitronectin receptor (VNR). Serum immunoreactive integrin levels were measured using these EIAs in various liver and malignant diseases. In almost all cases of liver cirrhosis (LC) and hepatocellular carcinoma (HCC), serum integrin levels were significantly elevated, but were in the normal range in gastric, colon, lung cancer, and acute hepatitis (AH). The correlation between serum FNR and VNR levels was statistically significant in all cases of liver disease, and no correlation was observed between these integrin levels and conventional biochemical markers such as AST, ALT, and GGT. The serum integrin levels were demonstrated to be a potential diagnostic marker for hepatic fibrogenesis and carcinogenesis, and these sandwich EIAs could be useful for determination of these integrins in clinical laboratory tests.

Animals↗
PubMed1992

Induction of alpha v beta 3 integrin-mediated attachment to extracellular matrix in beta 1 integrin (CD29)-negative B cell lines.

beta 1 integrin containing complexes have been implicated as the primary adhesion structures in many lymphocyte extracellular matrix (ECM) interactions. However, many B lymphocytes lack surface expression of the beta 1 subunit, implying that this subpopulation of lymphoid cells must employ alternate adhesion structures if they are to maintain an interactive capacity with ECM. An examination of the adherence properties of the beta 1 integrin-negative B cell line JY indicated that these cells exhibit little or no basal adherence to any of the ECM components examined. However, these cells could be induced to adhere to the ECM components fibronectin, laminin, and vitronectin following treatment with PMA. Blocking studies with monoclonal antibodies indicated the alpha v beta 3 integrin complex was involved in the attachment to each of these ligands. However, the adherence to fibronectin displayed a complex pattern of inhibition suggesting the involvement of other ECM receptors. The utilization of the alpha v beta 3 complex was not unique to the JY cell line. Other B cell lines were observed to employ alpha v beta 3, and these lines similarly lacked expression of beta 1 integrin. These results indicate that alpha v beta 3 can act as a lymphoid ECM-adhesion structure which may provide an alternative means for lymphocytes to interact with ECM. Furthermore, these studies provide evidence for the presence of lymphoid-associated alpha v beta 3 integrins with regulatable activity, which contrasts with the constitutive adhesive potential of these complexes when present on other cell types.

Antibodies, Monoclonal↗
PubMed1996

A mimetic of the RGDF-peptide [arginine-glycine-aspartic acid-phenylalanine] blocks aggregation and flow-induced platelet deposition on severely injured stenotic arterial wall. Effects on different animal models and in humans.

8-Guanidino-octanoyl-aspartic acid-phenylalanine (SC-49992), a mimetic of the tetrapeptide arginine-glycine-aspartic acid-phelylalanine, inhibits fibrinogen and vitronectin binding to GP IIb/IIIa. SC-49992 effects on impedance and optical aggregation were compared in different species (human, porcine and dog), SC-49992 induced significant inhibition both in whole blood and PRP aggregation, in all species; however, porcine platelets had a SC-49992 IC50 = 2.5 mM while human and dog platelets had a significant lower IC50 (1 microM and 1.5 microM, respectively). Inhibition of flow-mediated platelet deposition on severely injured vessels was studied in porcine blood at high and low shear rates for 5 minutes. Additionally, studies were performed in vessels with 80% stenosis. SC-49992 reduced platelet deposition both at high and low shear rate in parallel streamlined flow and in stenotic conditions. The lower affinity of porcine platelets for SC-49992 seems to be due to a species difference at the GPIIb/IIIa receptor RGD-sequence level.

Amino Acid Sequence↗
PubMed2004

Solid-phase synthesis of a small library of 3-phenylthio-3-nicotinyl propionic acid derivatives acting as antagonists of the integrin alphaVbeta3.

We describe the synthesis of a series of low molecular weight inhibitors of the alphavbeta3 integrin obtained by modifying a high-throughput screening hit with micromolar activity. A solid phase synthesis to prepare 3-phenylthio-3-nicotinyl propionic acid derivatives, exemplified by 13c, was set up. Compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit cell adhesion mediated by vitronectin have been obtained.

Cell Adhesion↗