Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported on the altered expression of a third actin in mouse-B16 melanoma associated with malignant progression. While further investigating the relationship of cytoskeletal proteins to malignancy, we found that the expression of vinculin was higher in weakly metastatic B16-F1 cells than in highly metastatic B16-F10 cells. By Northern blot analysis, the mRNA expression of vinculin in B16-F1 was also shown to be higher than in B16-F10. Immunofluorescence staining showed a clear dotted distribution of vinculin in B16-F1, but only a weak and diffuse distribution in B16-F10. The dotted distribution tended to be larger in B16-F1 and when cultured on Matrigel and fibronectin than on laminin and type IV collagen. An alteration in the expression of vinculin was also observed in other cell systems. Vinculin was detected in both normal 3Y1 and in relatively weakly malignant transformed 3Y1 cell lines, while vinculin was either scarcely detected or not detected at all in more malignant cell lines. These results suggest that the suppression of vinculin is closely related to malignant progression in both the B16-melanoma and 3Y1 cell systems.
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PMID:Differential expression of vinculin between weakly and highly metastatic B16-melanoma cell lines. 164 65

Using the avidin-biotin complex immunoperoxidase technique and antibodies to myoglobin, desmin, CLA, NSE, GFAP, keratin, fibronectin, alpha 1AT, lysozyme, S-100 protein, vimentin, cytokeratin, actin, the authors studied 60 cases of rhabdomyosarcoma (RMS) histopathologically diagnosed previously. Thirty-six cases showed both myoglobin and desmin positive stain, an objective evidence of the origin from skeletal muscles. The other 24 cases were identified as of non-skeletal muscle origin, including MFH, lymphoma, melanoma, neuroblastoma, malignant neurilemmoma, leiomyosarcoma etc. This study strongly suggests that histologic examination of RMS may lead to incorrect diagnosis. Histologically MFH and other types of spindle cell sarcomas invading normal skeletal muscles may be confused with pleomorphic RMS, lymphoma and neuroblastoma may be confused with embryonic RMS. Our findings indicate that myoglobin is a highly sensitive and specific tumor marker for RMS.
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PMID:[Immunohistochemical differential diagnosis of 60 cases of rhabdomyosarcoma]. 166 97

A human malignant melanoma cell line, Melur, secretes several glycoproteins that contain a unique carbohydrate epitope shared by neural cell adhesion molecules and recognized by the monoclonal antibodies HNK-1, L2, and 10C5. In this report, we present evidence that one of the major melanoma glycoproteins containing the HNK-1/10C5 epitope is the cell adhesion molecule, fibronectin, or a fibronectin-like molecule. Melanoma-derived fibronectin was isolated from serum-free conditioned medium by gelatin-Sepharose affinity adsorption and shown to react with monoclonal antibodies HNK-1 and 10C5 in Western blot analysis. HNK-1-containing fibronectin was purified on a gelatin-Sepharose column followed by an affinity column using a monoclonal antibody against the HNK-1 carbohydrate. The purified HNK-1-fibronectin then could be incorporated into the extracellular matrix of hamster fibroblasts in vitro, and such a matrix was detectable using the HNK-1 monoclonal antibody in an immunofluorescence assay. Of the seven neuroectoderm-derived tumor cell lines tested, only the Melur melanoma cell secreted fibronectin containing the HNK-1 carbohydrate. Identification of human neuroectoderm-derived fibronectin as a potential carrier of the HNK-1 carbohydrate suggests a new role for fibronectin in neural development and regeneration, and represents a new model for studying the function of this carbohydrate domain in neural cell adhesion.
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PMID:Human neuroectoderm-derived cell line secretes fibronectin that shares the HNK-1/10C5 carbohydrate epitope with neural cell adhesion molecules. 168 16

We have investigated the anti-angiogenic effect of a polymeric peptide based on the Arg-Gly-Asp (RGD) core sequence of fibronectin as a monomer unit, i.e., poly(RGD), in syngeneic mice and in vitro. Single intratumoral administration of poly(RGD) on day 0, 1 or 7 after tumor implantation achieved a significant reduction of B16-BL6 melanoma colonization in the lungs, but did not affect the size of the primary tumor at the time of amputation. The number of capillary blood vessels oriented toward the tumor mass increased during the early growth phase after the intradermal inoculation of the tumor. Poly(RGD) significantly inhibited the formation of tumor neovascularization when co-injected with the tumor cells or separately injected intratumorally or intravenously on day 1 or 3 after tumor inoculation. This inhibitory effect of poly(RGD) was dose-dependent. Poly(RGD) was able to inhibit the haptotactic migration of endothelial cells along a gradient of substratum-immobilized fibronectin but not laminin. Tumor-conditioned medium (CM) by itself did not act as a chemoattractant when it was added in the lower compartment of a Transwell chamber, but promoted the endothelial cell migration to immobilized fibronectin or laminin. Poly(RGD) inhibited the enhanced cell migration to fibronectin but not to laminin in response to CM. Thus, poly(RGD)-mediated inhibition of tumor metastasis may be partly due to the inhibition of tumor-induced angiogenesis at primary and secondary sites.
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PMID:Inhibition of tumor angiogenesis by a synthetic cell-adhesive polypeptide containing the Arg-Gly-Asp (RGD) sequence of fibronectin, poly(RGD). 169 94

The distribution of the extracellular matrix (ECM) glyco-protein tenascin (TN) has been evaluated immunohistochemically in benign and malignant lesions of the melanocytic lineage. Results of our study show that TN is detectable in a variety of benign and malignant lesions. In primary melanomas, TN displays a heterogeneous distribution, and a higher degree of expression of this glycoprotein is seen in lesions of greater dermal invasiveness. TN expression does not correlate with that of other ECM glycoproteins such as fibronectin. In vivo and in vitro experiments have also demonstrated that melanoma cells are capable of producing and releasing TN in the extracellular milieu.
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PMID:Expression and production of tenascin in benign and malignant lesions of melanocyte lineage. 169 27

The vitronectin receptor (alpha v beta 3) is a member of the integrin superfamily of adhesive protein receptors that mediate a wide spectrum of adhesive cellular interactions, including attachment to vitronectin, von Willebrand factor, fibrinogen, and thrombospondin. We have studied the binding of fibronectin to the purified vitronectin receptor, and the role of this receptor in the attachment of cells to fibronectin. A solid-phase microtiter assay was developed to investigate the binding properties of the vitronectin receptor. Purified alpha v beta 3 bound fibronectin with high affinity in a saturable, divalent cation-dependent manner. Binding was inhibited by soluble vitronectin, by RGD-containing peptides, and by LM609, a monoclonal antibody against the vitronectin receptor known to inhibit the binding of adhesive proteins to alpha v beta 3. Immunoinhibition experiments showed that M21 human melanoma cells, which express the fibronectin receptor, alpha 5 beta 1, as well as alpha v beta 3, used both of these integrins to attach and spread on fibronectin. In support of this finding, M21-L cells, a variant cell line that specifically lacks alpha v beta 3 but expresses alpha v beta 1, attached and spread poorly on fibronectin. In addition, alpha v beta 3 from surface-labeled M21 cells was retained, and selectively eluted by RGDS from a fibronectin affinity column. These results indicate that alpha v beta 3 acts in concert with alpha 5 beta 1 in promoting fibronectin recognition by these cells. We conclude that fibronectin binds to the alpha v beta 3 vitronectin receptor specifically and with high affinity, and that this interaction is biologically relevant in supporting cell adhesion to matrix proteins.
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PMID:The vitronectin receptor alpha v beta 3 binds fibronectin and acts in concert with alpha 5 beta 1 in promoting cellular attachment and spreading on fibronectin. 170 45

Glycoprotein IIb-IIIa (alpha IIb beta 3) and the vitronectin receptor (alpha v beta 3), two integrins that share the common beta 3 subunit, have been reported to function as promiscuous receptors for the RGD-containing adhesive proteins fibrinogen, vitronectin, fibronectin, von Willebrand factor, and thrombospondin. The present study was designed to establish a cell system for the expression of either GP IIb-IIIa or the vitronectin receptor in an otherwise identical cellular environment and to compare the adhesive properties of these two integrins with those of native GP IIb-IIIa and the vitronectin receptor constitutively expressed in HEL cells or platelets. M21 human melanoma cells lack GP IIb-IIIa and use the vitronectin receptor to attach to vitronectin, fibrinogen, fibronectin, and von Willebrand factor. To study the functional properties of GP IIb-IIIa in these cells, we transfected GP IIb into M21-L cells, a variant of M21 cells (Cheresh, D.A., and R.C. Spiro. 1987. J. Biol. Chem. 262:17703-17711), which lack the expression of functional alpha v and are therefore unable to attach to vitronectin, fibrinogen, and von Willebrand factor. Transfectants expressing GP IIb were isolated by immunomagnetic beads and surface expression of the GP IIb-IIIa complex was documented by FACS analysis and immunoprecipitation experiments performed with 125I-labeled M21-L/GP IIb cells. Comparative functional studies demonstrated that GP IIb-IIIa expressed in M21-L/GPIIb cells as well as native GP IIb-IIIa constitutively expressed in HEL-5J20 cells (an HEL variant lacking alpha v beta 3) mediated cell attachment to immobilized fibrinogen, but not to vitronectin or von Willebrand factor, whereas the vitronectin receptor expressed in M21 cells and HEL-AD1 cells (an HEL variant expressing alpha v beta 3) mediated cell attachment to fibrinogen, vitronectin, and von Willebrand factor. Similarly, PGl2-treated resting platelets attached to immobilized fibrinogen but not to vitronectin or von Willebrand factor, and this attachment could be inhibited by mAb A2A9 (directed against a functional site on the GP IIb-IIIa complex). However, in contrast to platelets, which adhered to vitronectin and von Willebrand factor after stimulation by thrombin or PMA, activation of the protein kinase C pathway in M21-L/GP IIb or HEL cells did not induce cell adhesion to vitronectin or von Willebrand factor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adhesive properties of the beta 3 integrins: comparison of GP IIb-IIIa and the vitronectin receptor individually expressed in human melanoma cells. 170 57

By sequencing cDNA clones which cover the complete coding region of human tenascin (TN), we have established its primary structure. This confirms that, as in the case of chicken, TN is mainly made up of three groups of sequences with a high homology to Epidermal Growth Factor (EGF) fibronectin (FN) type III repeat and fibrinogen. Furthermore, we have determined the amino-terminal sequence of the mature peptide directly on purified TN. The main differences with respect to the chicken TN molecule are that in the human there are 14 and half EGF-like repeats compared to 13 and half in the chicken and that, as previously reported, there are 15 FN-like repeats compared to 11 in the chicken. By Polymerase Chain Reaction (PCR) amplification we have also studied the different splicing patterns of the TN pre-mRNA in cultured cells. The results show the presence of at least four different isoforms containing different numbers of FN-like type III repeats. Using purified human TN as immunogen, we have obtained numerous monoclonal antibodies (Mabs) to TN. By screening a human melanoma cDNA library in the expression vector lambda gt11 with these Mabs and subsequently sequencing the insert of the positive clones, we have been able to localize, within the TN molecule, the epitopes recognized by two of these Mabs: BC-4, which recognizes an epitope within the EGF-like sequence and BC-2 which recognizes an epitope within the FN like type III repeats whose expression is regulated by alternative splicing of the TN pre-mRNA. Thus, while the Mab BC-4 may be useful in studies on TN distribution (since it recognizes all different TN isoforms) BC-2 may be useful in the study of the expression of particular TN isoforms generated by the alternative splicing of the TN primary transcript.
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PMID:Human tenascin: primary structure, pre-mRNA splicing patterns and localization of the epitopes recognized by two monoclonal antibodies. 170 64

35 intracranial tumours, 18 gliomas, 12 meningiomas, one neurilemmoma (neurinoma), one malignant melanoma and two metastases were successfully grown in-vitro and were submitted to immunocytochemical reactions, including cytokeratin, glial fibrillary acid protein (GFAP), vimentin, fibronectin, S-100 protein, neurofilament proteins, neuron-specific enolase (NSE) and basic myelin protein (MBP). Cytokeratin in metastases, GFAP and vimentin in gliomas, vimentin in meningiomas were consistently positive. S-100 protein was weakly and partially positive in gliomas, meningiomas, the neurilemmoma and malignant melanoma. Positive demonstration of fibronectin within cells was interpreted as a consequence of phagocytosis, except in meningiomas where fibronectin expression next to cell membranes seemed genuine. All other tested markers proved negative. The most important result seems to be that cells expressed markers irrespective of cellular shape and cytological morphology. It can be concluded that the cellular population as a whole consisted of tumour cells during the short time under observation and that supportive cell contamination during this early growth period was negligible.
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PMID:Routine immunohistochemical characterization of short term in vitro explants from human intracranial tumours. 170 42

Several kinds of cyclic peptides containing an L-arginine-glycine-L-aspartic acid RGD sequence were synthesized by the liquid phase method, and we investigated their effects on the attachment of mouse B16 melanoma cells onto fibronectin-coated well. Cyclo (GRGDSPA) inhibited the cell attachment at a 20-fold lower concentration than the linear form. The cell adhesion was inhibited by the synthetic peptides with the following relative order of activity: cyclo (GRGDSPA) much greater than cyclo (GRGD) greater than cyclo (RGDS), cyclo (GRGDSP) greater than cyclo (GRGDS) greater than cyclo (RGDSP), cyclo (RGDSPA). Cyclo (GRGDSPA) was more effective at inhibiting cell attachment to vitronectin than it was at competing with fibronectin attachment, as reported in the case of GRGDSP. Moreover, cyclo (GRGDSPA) significantly reduced the formation of colonies in mice injected with B16-FE7 melanoma cells.
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PMID:Effect of cyclic RGD peptide on cell adhesion and tumor metastasis. 171 Apr 55


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