Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of beta 1 integrins in neurite outgrowth following N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dBcAMP) treatment was investigated using the human neuroblastoma cell line TR 14. Three beta 1 integrins were identified: the alpha 1 beta 1 receptor bound collagen type I, collagen type IV and probably laminin; the alpha 2 beta 1 integrin bound collagen type I; and the alpha v beta i receptor bound fibronectin. Neurite extension was detectable as early as 30 minutes following dBcAMP treatment, was maximal after 24 hours and remained constant during treatment for 4 days. Adhesion-perturbing beta 1 subunit-specific antibodies, added together with dBcAMP, prevented the outgrowth of new neurites. During the first 24 hours of neurite outgrowth, no change was observed in the amount of beta 1 integrins nor in their topographic distribution. However, dBcAMP treatment increased the binding of alpha 1 beta 1 receptors to collagen type IV-Sepharose by a factor 2.3 +/- 0.6 (P < 0.02), while no alteration in the binding to collagen type I was detected. Moreover, neurites and growth cones were immunoreactive for collagen type IV but not for collagen type I. Consistently dBcAMP-induced neurite outgrowth was inhibited by adhesion-perturbing alpha 1 subunit-specific antibodies. Following maximal neurite outgrowth, the amount of beta 1 integrins determined by immunoprecipitation and by confocal microscopy decreased to 58.3 +/- 11.2% (P < 0.001) and to 55.4 +/- 17.5% (P < 0.001) of untreated levels, respectively, without any change in the level of beta 1 mRNA or de novo synthesized beta 1 precursor. However, pulse-chase experiments showed an increased turnover of the beta 1 subunit: the amount of beta 1 precursor that was degraded after 1 hour chase was 50.5 +/- 8.4% in cells treated for 4 days and 34.2 +/- 3.9% in untreated cells (P < 0.02); the amount of mature beta 1 after 24 hours chase was smaller in cells treated for 4 days compared to untreated cells. In conclusion, during neurite outgrowth, alpha 1 beta 1 integrins are required and acquire an enhanced binding activity for collagen type IV; but following maximal neurite outgrowth, expression of beta 1 integrins is reduced.
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PMID:Selective increase in the binding of the alpha 1 beta 1 integrin for collagen type IV during neurite outgrowth of human neuroblastoma TR 14 cells. 753 84

The beta 1 integrin subfamily, alternatively called very late activation antigen (VLA), has been implicated in various cellular functions. In this study, we generated a mAb against the mouse beta 1 subunit (CD29) to examine the functional property of mouse VLA proteins. After immunization with affinity-purified mouse VLA-4 (alpha 4 beta 1), a hamster mAb, HM beta 1-1, was established by screening mAb that reacted with alpha 4-negative neuroblastoma C1300. The antigen defined by HM beta 1-1 was widely distributed in various mouse cell lines and HM beta 1-1 immunoprecipitated a 110-120 kDa protein common to VLA-1 and VLA-6, indicating that HM beta 1-1 recognizes the beta 1 subunit of mouse integrins. We then examined the inhibitory effect of HM beta 1-1 on VLA-dependent cell adhesion and activation. HM beta 1-1 blocked the adhesion of mouse tumor cell lines to extracellular matrix proteins including collagen, laminin and fibronectin. Moreover, splenic T cell proliferation induced by anti-CD3 mAb and allogeneic mixed lymphocyte response were strongly inhibited by HM beta 1-1 in combination with an anti-LFA-1 mAb. We conclude that HM beta 1-1 reactive with mouse CD29 can inhibit VLA-dependent cellular functions and, thus, would be useful for studying the physiological role of beta 1 integrins in vivo.
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PMID:Identification and functional characterization of mouse CD29 with a mAb. 754 9

Integrins belong to a large family of heterodimeric membrane glycoproteins which mediate cell-cell or cell-extracellular matrix interactions. These interactions could play a major role during the migration of tumor cells across the extracellular matrix and vascular endothelium and would thus appear to be requisite for the metastatic process. Pretreatment of the Foss human melanoma cell line with HILDA/LIF or OSM, two cytokines involved in acute-phase response, increased the expression of membrane alpha v beta 1 1.5-2-fold. The same phenomenon was observed on the SK-N-SH human neuroblastoma cell line. alpha v beta 1 upmodulation was concomitant with improved tumor cells attachment to the fibronectin matrix. This greater adhesion of tumor cells to fibronectin was inhibited by specific monoclonal antibodies against alpha v or beta 1 integrin subunits. Similar results were obtained after TNF-alpha treatment. Our findings demonstrate the ability of HILDA/LIF and OSM to modulate tumor cell capacity to adhere to the matrix component, suggesting a potential role for these cytokines in modulation of tumoral progression.
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PMID:Upmodulation of alpha v beta 1 integrin expression on human tumor cells by human interleukin for DA cells/leukemia inhibitory factor and oncostatin M: correlation with increased cell adhesion on fibronectin. 759 53

Alzheimer's-afflicted neurons contain phosphorylated forms of tau that are not present in healthy adults. these can be recognized with great specificity by monoclonal antibodies such as paired helical filament-1 (PHF-1) [Greenberg S. G. and Davies P. (1990) Proc. natn. Acad. Sci. U.S.A. 87, 5827-5831; Greenberg S. G. et al. (1992) J. biol. Chem. 267, 564-569]. The PHF-1 phospho-tau epitope is also present in immature neurons undergoing axodendritic differentiation [Pope W. B. et al. (1993) Expl Neurol. 120, 106-113]. Analogous to its presence in immature neurons, we report here that the PHF-1 tau epitope spontaneously occurs in the human neuroblastoma cell line SHSY5Y, where its level can be regulated by differentiation and by molecules found in the extracellular matrix. Confocal immunofluorescence studies showed PHF-1 epitope to be constitutively expressed in the somatic cytoplasm as well as in short neurites typical of undifferentiated SHSY5Y cells. Induction of differentiation with retinoic acid produced cells with a neuronal morphology and a redistribution of the expression of PHF-1 tau in the long neurites. Protracted exposure to retinoic acid decreased the levels of PHF-1 immunofluorescence without a loss of neurites, similar to the developmental down-regulation seen in situ. The effects of retinoic acid on PHF-1 immunofluorescence were modifiable by fibronectin, which can be released by some neuroblastoma cell lines [Ciccarone V. et al. (1989) Cancer Res. 49, 219-225; Yoshihara T. et al. (1992) Int. J. Cancer 51, 620-626]. Exogenous human fibronectin caused a marked up-regulation of PHF-1 immunofluorescence. Quantitative analysis of 15 multicellular areas, from six different cultures, per experimental condition showed a 16-fold increase compared to untreated controls. Up-regulation by fibronectin was also evident in undifferentiated cells. Cell counts indicated no proliferative effects of the fibronectin under the conditions used. Laminin also caused an increase of PHF-1 tau in retinoic acid-treated cells. Data obtained from immunoblots verified the results observed with immunofluorescence. The data show that the PHF-1 tau epitope is spontaneously expressed by non-degenerating human neuroblastoma cells, down-regulated by cellular differentiation, induced by retinoic acid and up-regulated by the extracellular matrix components fibronectin and laminin. One explanation of the data is that fibronectin maintains a population of SHSY5Y cells in a biochemical state of differentiation in which PHF-1 tau is expressed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alzheimer's-associated phospho-tau epitope in human neuroblastoma cell cultures: up-regulation by fibronectin and laminin. 765 8

Two human neuroblastoma cell lines, LAN-5 and GI-CA-N, have been analyzed for their capability to adhere to different extracellular matrix (ECM) components. The GI-CA-N cells adhered to all the tested substrates: laminin (LN), type I and type IV collagen (Coll I, Coll IV), vitronectin (VN), and fibronectin (FN). Conversely LAN-5 cells weakly attached to FN and VN, whilst adhesion on LN and Coll I and IV was strong and induced a rapid elongation of cell processes. By means of RT-PCR and immunoprecipitation we showed that the integrin pattern of these two lines was different and could explain their diversity in adhesion capability. Both cell lines express a large amount of the beta 1 integrin subunit, associated with different alpha chains, probably responsible for their adhesion to some ECM proteins. After treatment of LAN-5 cells with biological differentiating agents, such as gamma-interferon, alone or in combination with tumour necrosis factor-alpha (TNF-alpha), or retinoic acid, the levels of alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 integrin expression were enhanced, while the amount of alpha v remained constant. In contrast, treatment of LAN-5 cells with TNF-alpha, that did not induce any maturation, or starvation in 2% foetal calf serum, that inhibited cell proliferation without affecting neural differentiation, did not induce any change in the integrin assessment. Messenger-RNAs for the two alpha 6 isoforms, A and B, were present in both cell lines. However, in LAN-5 cells, the protein product was neither detectable nor inducible by differentiation. Our results confirm the specific modulation of the alpha 1 beta 1 integrin expression in human neuronal development, and show, for the first time, the involvement of alpha 2 beta 1 and alpha 3 beta 1 heterodimers in this maturational process.
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PMID:Modulation of alpha 1 beta 1, alpha 2 beta 1 and alpha 3 beta 1 integrin heterodimers during human neuroblastoma cell differentiation. 769 64

beta-Amyloid accumulates as extracellular aggregates in Alzheimer's-afflicted brain tissue, but it also is secreted by healthy tissue, for reasons not yet established. One possibility is that beta-amyloid, which contains a sequence (RHDS) homologous to the cell-binding domain of fibronectin, may modulate integrin function, a possibility supported by previous data from non-neuronal cells (Ghiso et al., Biochem. J., 288 (1992) 1053-1059). The current work shows that functional interaction with beta-amyloid peptides is also supported by integrins in neuronal cells. Experiments used the SH-SY5Y human neuroblastoma cell line, which was shown to contain integrins that mediated cell adhesion to substratum-bound fibronectin. Adhesion to fibronectin was partially blocked by synthetic beta-amyloid peptides containing the RHDS sequence. beta-Amyloid sequences adsorbed to substratum themselves were found to mediate cell adhesion, although less effectively than fibronectin. Anti-integrin blocked the peptide-mediated adhesion, at doses commensurate with those blocking fibronectin-mediated adhesion. The data support the hypothesis that beta-amyloid peptides could physiologically, and perhaps pathogenically, modulate the activity of neuronal integrins, important cell surface receptors known to control protein kinase activities, Ca2+ levels, gene expression and organization of the cytoskeleton.
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PMID:Interaction of beta-amyloid peptides with integrins in a human nerve cell line. 773 99

We have developed a method for promoting cell aggregation with bifunctional macromolecules synthesized by coupling cell-binding peptides to an inert, water-soluble polymer. The peptides Arg-Gly-Asp (RGD) and Tyr-Ile-Gly-Ser-Arg (YIGSR) were conjugated through their amino termini to both ends of linear poly(ethylene glycol) (PEG), producing bifunctional hybrid polymers: RGD-PEG-RGD and YIGSR-PEG-YIGSR. RGD-PEG-RGD promoted aggregation of mechanically-dissociated fetal brain cells, pheochromocytoma cells (PC12), and neuroblastoma cells maintained in rotation culture at 37 degrees C. Enhanced aggregation was noticeable within 10 minutes and became more pronounced over the next several hours: after 7-9 hours, the mean aggregate volume was up to 10 times larger than the mean volume produced in suspensions containing unmodified PEG. Similar results were obtained with YIGSR-PEG-YIGSR and PC12 cells. Enhancement in aggregation correlated with the ability of soluble RGD or YIGSR to inhibit cell adhesion to surfaces coated with laminin or fibronectin. This method for promoting aggregation may be useful for large scale culture of anchorage dependent cells, eliminating the need for microcarriers. In addition, aggregates formed by this method may be suitable for use in artificial organs or as cell transplants for tissue regeneration.
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PMID:Cell-binding peptides conjugated to poly(ethylene glycol) promote neural cell aggregation. 776 20

Differentiated human neuroblastoma LA-N1 cells that were exposed to dibutyryl adenosine 3',5'-cyclic monophosphate for 5 days (primed cells) showed increased adhesion to laminin-, fibronectin-, and collagen type I-coated plates as compared to unprimed cells. Moreover, primed cells seemed to adhere best to laminin. The binding site in laminin, mediating cell attachment, was identified as containing the YIGSR sequence, a known cell binding motif, located in the short arm of the B1 chain of laminin. The synthetic peptide amide, C(YIGSR)3-NH2, containing a repeat of this binding motif, inhibited the attachment of neuroblastoma cells to laminin in a competitive manner, and its inhibitory activity was inversely dependent on laminin concentrations. Affinity chromatography of membrane-extracted proteins over an Affi-Gel 10 column conjugated to C(YIGSR)3-NH2, revealed a major YIGSR-binding protein with an apparent molecular mass of 67 kDa. The 67-kDa surface membrane protein was specifically eluted from the column with the soluble C(YIGSR)3-NH2 peptide, but not with an unrelated peptide. Furthermore, no 67-kDa laminin-binding protein was recovered from an unrelated peptide matrix with the free C(YIGSR)3-NH2 peptide. Ligand blot overlay assays with biotin-labeled C(YIGSR)3-NH2 peptide demonstrated that the 67-kDa receptor is indeed a YIGSR-binding protein. This 67-kDa laminin-binding protein appeared to be down-regulated upon differentiation of LA-N1 cells, as indicated by the level of this protein and its mRNA.
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PMID:Down-regulation of a 67-kDa YIGSR-binding protein upon differentiation of human neuroblastoma cells. 776 44

Three human neuroblastoma cell lines, with or without N-myc amplification, were evaluated for their integrin expression patterns as cultured cells, as well as their nude mouse-borne tumors obtained after subcutaneous (ectopic) or adrenal gland (orthotopic) injection. IMR-32 and LaN1 cells (with amplified N-myc) do not express any of the common integrin subunits that recognize fibronectin or collagens, as determined by immunoprecipitation of cell extracts with specific monoclonal antibodies; the same was true for all subcutaneous or adrenal tumors from IMR-32 or LaN1, indicating that they are not essential during primary tumor formation at either site. SK-N-SH cells (with diploid N-myc) express beta 1, alpha 2, and alpha 3 subunits of expected sizes (with alpha 2 uncleaved at 145 kDa) but do not express alpha 1, alpha 4, alpha 5, alpha V, or beta 3. This expression pattern was conserved in all first-round subcutaneous and adrenal tumor cell populations, as well as in second-round subcutaneous tumors derived from a first-round subcutaneous tumor (no tumors expressed beta 3). One significant difference was noted between subcutaneous and adrenal tumor populations: all first- and second-round subcutaneous tumors expressed high levels of alpha V subunit, while adrenal tumors did not express any alpha V. This result suggests some essential function for alpha V beta 1 during subcutaneous primary tumor formation. Integrin patterns were also evaluated by fluorescence-activated cell sorting. SK-N-SH and its derivative tumors expressed heterogeneous amounts of beta 1 and alpha 2 at the cell surface, while only subcutaneous tumor cells expressed alpha V. Parental SK-N-SH cells contained two subpopulations, half of which expresses alpha 3, while the other half does not; all subcutaneous tumor cells retained this two-subpopulation pattern, indicating that primary tumor formation does not lead to clonal dominance of alpha 3- or alpha 3+ cell types in larger primary tumors. While these results suggest a correlation between N-myc amplification and down-regulation of integrin expression in neuroblastoma, they demonstrate conservation of integrin expression during two rounds of primary tumor formation at ectopic or orthotopic sites in a mouse model system, induction and/or selection for alpha V beta 1 expression at the subcutaneous site, and clonal heterogeneity in alpha 3 beta 1 expression throughout primary tumor development.
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PMID:Integrin expression in human neuroblastoma cells with or without N-myc amplification and in ectopic/orthotopic nude mouse tumors. 802 May 86

The DCC (deleted in colorectal cancer) gene was identified because it is affected by somatic mutations in colorectal tumors, including allelic losses in greater than 70% of cancers and localized mutations in a subset of cases. The DCC gene also may be inactivated in other tumor types, including cancers of the pancreas, stomach, breast, prostate, and brain, as well as some leukemias. We have characterized DCC complementary DNAs obtained from human fetal brain tissues and IMR32 human neuroblastoma cells. Based on the fetal brain complementary DNA sequence, the predicted transmembrane DCC protein product has 1447 amino acids. The extracellular domain of about 1100 amino acids has four immunoglobulin-like domains and six fibronectin type III-like domains; the 325-amino acid cytoplasmic domain does not show similarity to previously characterized proteins. Comparison of DCC complementary DNAs from IMR32 cells to those from fetal brain identified two potential alternative splice sites. Studies of adult mouse tissues revealed that DCC transcripts were present at very low levels in all tissues studied, and alternative splicing of DCC transcripts was seen in some tissues. Immunoblotting and immunoprecipitation studies with DCC-specific antisera identified protein species with molecular weights of approximately 175,000-190,000 in some rodent tissues and human tumor cell lines. DCC protein expression was highest in brain tissues and neural crest-derived cell lines and markedly reduced or absent in the majority of cancer cell lines studied. Treatment of DCC-expressing cells with tunicamycin decreased the apparent molecular weight of the immunoreactive proteins, establishing that DCC is a glycoprotein. The studies presented here demonstrate that the DCC gene encodes several related glycoprotein species that are likely to be expressed at very low levels in many normal adult tissues. Furthermore, the absence of DCC expression in some of the cancer cell lines studied may result from genetic inactivation of DCC.
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PMID:Expression and alternative splicing of the deleted in colorectal cancer (DCC) gene in normal and malignant tissues. 804 1


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