concanavalin-a and Brain-Neoplasms

Epithelial-to-mesenchymal transition (EMT) recapitulates metastasis and can be induced in vitro through transforming growth factor (TGF)-β signaling. A role for MMP activity in glioblastoma multiforme has been ascribed to EMT, but the molecular crosstalk between TGF-β signaling and membrane type 1 MMP (MT1-MMP) remains poorly understood. Here, the expression of common EMT biomarkers, induced through TGF-β and the MT1-MMP inducer concanavalin A (ConA), was explored using RNA-seq analysis and differential gene arrays in human U87 glioblastoma cells. TGF-β triggered SNAIL and fibronectin expressions in 2D-adherent and 3D-spheroid U87 glioblastoma cell models. Those inductions were antagonized by the TGF-β receptor kinase inhibitor galunisertib, the JAK/STAT inhibitors AG490 and tofacitinib, and by the diet-derived epigallocatechin gallate (EGCG). Transient gene silencing of MT1-MMP prevented the induction of SNAIL by ConA and abrogated TGF-β-induced cell chemotaxis. Moreover, ConA induced STAT3 and Src phosphorylation, suggesting these pathways to be involved in the MT1-MMP-mediated signaling axis that led to SNAIL induction. Our findings highlight a new signaling axis linking MT1-MMP to TGF-β-mediated EMT-like induction in glioblastoma cells, the process of which can be prevented by the diet-derived EGCG.

Topics: Brain Neoplasms; Catechin; Cell Line, Tumor; Concanavalin A; Epithelial-Mesenchymal Transition; Fibronectins; Glioblastoma; Humans; Matrix Metalloproteinase 14; Piperidines; Pyrazoles; Pyrimidines; Quinolines; Receptors, Transforming Growth Factor beta; Signal Transduction; Snail Family Transcription Factors; STAT3 Transcription Factor; Transforming Growth Factor beta1; Tyrphostins

Pre-clinical trials for cancer therapeutics support the anti-neoplastic properties of the lectin from Canavalia ensiformis (Concanavalin-A, ConA) in targeting apoptosis and autophagy in a variety of cancer cells. Given that membrane type-1 matrix metalloproteinase (MT1-MMP), a plasma membrane-anchored matrix metalloproteinase, is a glycoprotein strongly expressed in radioresistant and chemoresistant glioblastoma that mediates pro-apoptotic signalling in brain cancer cells, we investigated whether MT1-MMP could also signal autophagy. Among the four lectins tested, we found that the mannopyranoside/glucopyranoside-binding ConA, which is also well documented to trigger MT1-MMP expression, increases autophagic acidic vacuoles formation as demonstrated by Acridine Orange cell staining. Although siRNA-mediated MT1-MMP gene silencing effectively reversed ConA-induced autophagy, inhibition of the MT1-MMP extracellular catalytic function with Actinonin or Ilomastat did not. Conversely, direct overexpression of the recombinant Wt-MT1-MMP protein triggered proMMP-2 activation and green fluorescent protein-microtubule-associated protein light chain 3 puncta indicative of autophagosomes formation, while deletion of MT1-MMP's cytoplasmic domain disabled such autophagy induction. ConA-treated U87 cells also showed an upregulation of BNIP3 and of autophagy-related gene members autophagy-related protein 3, autophagy-related protein 12 and autophagy-related protein 16-like 1, where respective inductions were reversed when MT1-MMP gene expression was silenced. Altogether, we provide molecular evidence supporting the pro-autophagic mechanism of action of ConA in glioblastoma cells. We also highlight new signal transduction functions of MT1-MMP within apoptotic and autophagic pathways that often characterize cancer cell responses to chemotherapeutic drugs.

Topics: Acridine Orange; Autophagy; Brain Neoplasms; Cell Line, Tumor; Concanavalin A; Fluorescent Dyes; Gene Expression Regulation, Neoplastic; Gene Silencing; Glioblastoma; Humans; Hydroxamic Acids; Indoles; Mannose; Matrix Metalloproteinase 14; Neoplasm Proteins; Protein Structure, Tertiary; RNA, Small Interfering; Signal Transduction; Vacuoles

Internalization, recycling, and resensitization of the human delta-opioid receptor (hDOR) were studied in the neuroblastoma cell line SK-N-BE, endogenously expressing this receptor. Conventional and confocal fluorescence microscopy observations, corroborated by Scatchard analysis, indicated that after a 100 nM Eto treatment, 60 to 70% of hDOR were rapidly internalized (t(1/2) < 15 min). This agonist-triggered internalization was reversible for a treatment not exceeding 1 h and became irreversible for prolonged treatment (4 h), leading probably to the degradation and/or down-regulation of the receptor. The rapid internalization of hDOR was totally blocked in the presence of heparin, known as an inhibitor of G protein-coupled receptor kinases (Benovic et al., 1989), a result indicating that phosphorylation by these kinases is a critical step in desensitization (Hasbi et al, 1998) and internalization of hDOR (present study) in SK-N-BE cell line. Blockade of internalization by agents not interferring with phosphorylation, as hypertonic sucrose or concanavalin A, also blocked the resensitization (receptor functional recovering) process. Furthermore, blockade of dephosphorylation of the internalized hDOR by okadaic acid totally suppressed its recycling to the plasma membrane and its subsequent resensitization. These results indicate that regulatory events leading to desensitization, internalization, and recycling in a functional state of hDOR involve phosphorylation by a G protein-coupled receptor kinase, internalization via clathrin-coated vesicles, and dephosphorylation by acid phosphatases.

Topics: Brain Neoplasms; Concanavalin A; Cyclic AMP; Diprenorphine; Heparin; Humans; Hypertonic Solutions; Immunohistochemistry; Microscopy, Confocal; Narcotic Antagonists; Neuroblastoma; Ovalbumin; Phosphorylation; Radioligand Assay; Receptors, Opioid, delta; Sucrose; Tumor Cells, Cultured

Maitotoxin (MTX) at 0.3 nM elicited a 10-20-fold increase in the level of Ca(2+) influx in rat glioma C6 cells. At higher doses (3-30 nM), MTX induced marked Ca(2+) influx in human erythrocyte ghosts when monitored with the fluorescent dye Fura-2. Although the ghosts were not as susceptible to MTX as intact erythrocytes or other cell lines, Fura-2 experiments under various conditions suggested that the MTX-induced entry of ions into the ghosts was mediated by a mechanism similar to that reported for cells or tissues. These ghosts are the simplest system known to be sensitive to MTX and thus may be suitable for research on the direct action of MTX. Gangliosides GM1 and GM3, glycosphingolipids which have a sialic acid residue, strongly inhibited MTX-induced Ca(2+) influx in C6 cells, while the inhibitory action by asialo-GM1, which lacks a sialic acid residue, was somewhat weaker. Their inhibitory potencies were in the following order: GM1 (IC(50) approximately 2 microM) > GM3 (IC(50) approximately 5 microM) > asialo-GM1 (IC(50) approximately 20 microM). GM1 (3 microM) completely blocked MTX (30 nM)-induced Ca(2+) influx in human erythrocyte ghosts. When C6 cells were pretreated with tunicamycin, an antibiotic which inhibits N-linked glycosylation, or concanavalin A, a lectin which exhibits a high affinity for cell-surface oligosaccharides, MTX-induced Ca(2+) influx was significantly potentiated. This suggests that removal of oligosaccharides from the cell surface by tunicamycin or capping of sugar chains on plasma membranes by concanavalin A can potentiate the action of MTX.

Topics: Animals; Anti-Bacterial Agents; Brain Neoplasms; Calcium; Calcium Radioisotopes; Concanavalin A; Erythrocyte Membrane; Fluorescent Dyes; Fura-2; Gangliosides; Glioma; Marine Toxins; Membrane Lipids; Membrane Potentials; Models, Molecular; Molecular Conformation; Oxocins; Rats; Tumor Cells, Cultured; Tunicamycin

18 cases of low-graded mixed gliomas were studied using the two lectins Concanavalin A (Con A) and Peanut lectin (PNA). Con A stained cytoplasm and processes of tumoral astrocytes, whereas PNA stained cell membranes of tumoral oligodendrocytes. Con A and PNA are reliable markers for astrocyte and oligodendrocyte areas of mixed gliomas, respectively. A part of cells were overlappingly positive for both lectins. They expressed an oligosaccharide pattern of both glioma types and represented a third, intermediate cell type of mixed gliomas. The existence of intermediate cells close to astrocytic and oligodendroglial cell types in mixed gliomas could result from transformation processes of neoplastic glial cells or from the malignant transformation of a common glial precursor cell.

Topics: Adult; Aged; Astrocytes; Brain Neoplasms; Concanavalin A; Female; Glial Fibrillary Acidic Protein; Glioma; Glucose; Humans; Male; Mannose; Middle Aged; Oligodendroglia; Peanut Agglutinin

Oligodendrogliomas (n = 26) induced by ethylnitrosourea (ENU) in wistar rats were examined to assess the lectin specificity to oligodendroglial membranes. Two different types of oligodendrogliomas were found in our material: an isomorphous type (n = 12), and a polymorphous type (n = 14). The first one, with two variants according to its size, macro- (n = 9) and microtumors (n = 3), had predominantly a honey-comb pattern with 'clear halos' around the nuclei without anaplasia. The second type, composed mostly by macrotumours, was anaplastic, with high cellular density, necrosis and intratumoral hemorrhages. Peanut agglutinin (PNA) labelled plasma membranes of well-differentiated cellular components of the first group. The tumoral oligodendrocytes lost the property to bind PNA in the second group of tumours, while Concanavalin A (Con A) showed affinity to intracytoplasmic structures of these tumours. PNA is a reliable marker of oligodendroglial plasma membrane of well-differentiated ENU-induced oligodendrogliomas. This experimental model, using PNA and Con A, may have important clinical applications regarding the biological behaviour of this type of neoplasm.

Topics: Animals; Brain; Brain Neoplasms; Carcinogens; Concanavalin A; Ethylnitrosourea; Immunohistochemistry; Lectins; Oligodendroglioma; Peanut Agglutinin; Rats; Rats, Wistar

In this study, we investigated the expression of activated gelatinase A and membrane-type metalloproteinase (MT-MMP) induced by concanavalin A (ConA) in four highly invasive glioma cell lines (UWR2, UWR3, U251MG, and SNB-19). We also examined gelatinase A and MT-MMP expression in human brain tumor tissues in vivo. Gelatin zymography showed that all four cell lines expressed latent progelatinase A (M(r) 66,000). Activated gelatinase A (M(r) 62,000) was induced by ConA in only UWR2 or UWR3 cells. MT-MMP mRNA was present in all four cell lines prior to ConA treatment, and the relative hybridization signals were 1, 0.80, 0.25, and 0.15 in UWR2, UWR3, U251MG, and SNB-19 cells, respectively. These mRNA signals were dramatically increased (2,8-, 5.4-, and 2.2-fold in UWR2, UWR3, and U251MG cells, respectively) following ConA treatment; however, MT-MMP mRNA expression was unchanged in SNB-19 cells. MT-MMP protein was detected in various amounts in the four cell lines, but only after ConA pretreatment. The amount of MT-MMP mRNA was unchanged in SNB-19 after ConA treatment, and the MT-MMP mRNA level in ConA-treated U251MG was lower than in UWR2 and UWR3 without ConA treatment. MT-MMP protein was detected in SNB-19 and U251 cell lines only after ConA treatment. Gelatin zymography of human brain tumor tissues revealed that almost all samples examined contained a latent form of gelatinase A, whereas the activated form of gelatinase A was only seen in metastatic lung adenocarcinomas and malignant astrocytomas, and especially in glioblastomas. MT-MMP mRNA levels were significantly higher in malignant astrocytomas than in low-grade gliomas and normal brain tissues. These results were confirmed by PCR analysis, which showed that MT-MMP mRNA was absent or barely detectable in normal brain white matter but was easily detectable in malignant astrocytomas. Immunohistochemistry of MT-MMP in frozen sections showed that MT-MMP was localized in neoplastic astrocytes of malignant astrocytomas but was undetectable in normal white brain matter. The data indicate that MT-MMP is present in malignant human glial tumors and that MT-MMP expression correlates with expression and activation of gelatinase A during malignant progression in vivo. A direct correlation between the levels of MT-MMP protein and its transcripts was not found in vitro, suggesting that MT-MMP expression in glioma cell lines might be regulated either at the level of transcription message stability or at posttranscrip

Topics: Astrocytoma; Base Sequence; Blotting, Northern; Blotting, Western; Brain; Brain Neoplasms; Concanavalin A; Disease Progression; Enzyme Activation; Enzyme Precursors; Fluorescent Antibody Technique; Gelatinases; Glioma; Humans; Immunohistochemistry; Matrix Metalloproteinase 2; Matrix Metalloproteinases, Membrane-Associated; Metalloendopeptidases; Molecular Sequence Data; Polymerase Chain Reaction; Proteins; Receptors, Cell Surface; Reference Values; RNA, Messenger; Tissue Inhibitor of Metalloproteinase-2; Tumor Cells, Cultured

An in vitro technique was developed to generate activated rat T cells, with antitumor activity. Splenic mononuclear cells (SMC) from outbred Wistar and inbred Wistar-Munich rats were stimulated with Concanavalin A and recombinant human interleukin-2 (rIL-2) in vitro for 48 h. After 2 days, the nonadherent cells began proliferating and were maintained in rIL-2 for up to 18 days in vitro. FACScan analysis revealed that SMC was a mixture of cell types; however, CD5+ T cells rapidly increased and became the predominant cell type after 5 days in culture. SMC induced cytolysis of YAC-1, but not C6 glioma cells in 4 h 51Cr release assays. In contrast, 5- and 9-day T cells lysed C6 glioma and YAC-1 cells. The C6 cells were admixed with cultured effector cells at various effector-to-target (E:T) ratios and were injected into the right cerebral hemisphere of Wistar and Wistar-Munich rats for a Winn assay. Histopathologic evaluations revealed that a) SMC had no effect; b) 2- and 5-day T cells, injected at E:T ratios greater than 5:1, caused significant reduction in tumor size; and c) 2- or 5-day T cells, at a 40:1 E:T ratio, resulted in little or no histologic evidence of tumor. Eighty-three percent of animals receiving C6 and 5-day mitogen-stimulated lymphokine activated killer cells at an E:T ratio of 40:1 were alive 120 days postinjection (p less than 0.05).

Topics: Animals; Brain Neoplasms; Cell Division; Cell Survival; Cells, Cultured; Concanavalin A; Glioma; Immunophenotyping; Immunotherapy, Adoptive; Interleukin-2; Killer Cells, Lymphokine-Activated; Lymphoma; Male; Neoplasm Transplantation; Rats; Rats, Inbred Strains; Recombinant Proteins; Spleen; Tumor Cells, Cultured

We have employed human Gl-As-14(S) brain tumour cell line to study antiproliferative action of retinoic acid (RA). RA (20 microM) caused a time-dependent, dose-dependent, cell seeding density-dependent reduction in cell proliferation in liquid medium and inhibited growth in agar. Growth inhibitory effects of RA were also affected by the concentration of fetal bovine serum (PBS) in the medium. All these effects could be reversed within 48 h after removal of RA from the growth medium. RA-treated cells also displayed reduced concanavalin A (Con A) binding ability by microhemadsorption technique. The results demonstrated that RA can suppress in this tumour cell line the expression of some properties frequently associated with transformed cells.

Topics: Antineoplastic Agents; Brain Neoplasms; Cell Aggregation; Cell Division; Concanavalin A; Culture Media; Dose-Response Relationship, Drug; Hemadsorption; Humans; Tretinoin; Tumor Cells, Cultured

Mononuclear cells infiltrating human brain tumors were isolated from seven of nine surgical biopsy specimens. These cells were small T11+, T3+ lymphocytes that did not express DR antigens or the receptor for interleukin-2. In addition, large granular lymphocytes were recovered from two of these tumors. The clonogenic potential of tumor-infiltrating lymphocytes (TIL's) was assessed by limiting-dilution analysis (LDA) using a microculture system that permits proliferation of virtually 100% of normal peripheral blood T lymphocytes (PBL-T's). In comparison to normal and autologous PBL-T's, TIL's had a strikingly reduced proliferative potential revealed by a decrease in the frequency of proliferating T lymphocyte precursors calculated by LDA. On average, only one of every 100 T cells from TIL's was able to proliferate, as compared to one of every two or all of the T cells from the patient's peripheral blood or from normal donors. Furthermore, the TIL populations showed depressed proliferative responses to the lectins phytohemagglutinin and concanavalin A and to the phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate. Clonal analysis performed on the proliferating microcultures from three tumors demonstrated that the majority of these clones possessed cytolytic activity against various tumor cell targets. Among clones tested for cytolytic activities with glioma cells, four lysed cultured autologous tumor cells, and the specific lysis was greater than 50% in all cases. Numerous clones with natural killer (NK)-like activity were obtained from two TIL preparations, and the frequency of cytolytic T lymphocyte precursors with NK-like activity was determined for one of these preparations and was found to be higher than that in the patient's peripheral blood. Glioma cells grown in culture and then mixed with normal peripheral blood lymphocytes (PBL's) were capable of inhibiting the PBL's response to lectins. This inhibitory property may account in part for the observed poor clonogenicity of TIL's from brain tumors. Nevertheless, nearly all proliferating clones displayed cytotoxicity against either autologous or allogeneic tumor cell targets and may imply selective accumulation of cytolytic effector cells at the tumor site.

Topics: Adult; Aged; Antibodies, Monoclonal; Brain Neoplasms; Cell Division; Child; Clone Cells; Concanavalin A; Cytotoxicity, Immunologic; Female; Glioma; Humans; Immunohistochemistry; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes; Tumor Cells, Cultured

In order to investigate the possibility that the theory of two-stage carcinogenesis can be applied to neurogenic carcinogenesis, we analyzed the promoting effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the in vitro malignant transformation of fetal rat brain cells exposed in utero to ethylnitrosourea (ENU). Rat brain cells were transferred to a cultured system at 72 h after a single pulse of ENU (50 mg/kg body weight) to pregnant SD-JCL rats on the 18th day of gestation. The positive findings of glial fibrillary acidic protein and S-100 protein in primary cultured cells by the analysis of immunohistochemistry revealed the neuroglial origin of transformed cells. These cells were divided into 12 groups and were treated twice per week with or without TPA at concentrations from 0.1 to 50.0 ng/ml. From the results of cellular morphology, Concanavalin A agglutinability, colony forming capacity in semisolid soft agar, and tumorigenicity in vivo, malignant transformation of fetal rat brain cells appeared earlier in the ENU group treated with TPA than in the untreated ENU group. On the basis of these observations, it is suggested that TPA might be effective as a tumor promoter on ENU-induced neurogenic carcinogenesis.

Topics: Animals; Brain Neoplasms; Cell Aggregation; Cell Division; Cell Transformation, Neoplastic; Cells, Cultured; Cocarcinogenesis; Concanavalin A; Ethylnitrosourea; Female; Glial Fibrillary Acidic Protein; Maternal-Fetal Exchange; Neoplasm Transplantation; Neoplastic Stem Cells; Phorbols; Pregnancy; Rats; Tetradecanoylphorbol Acetate

Immunosuppressive mechanisms in patients with malignant brain tumors were studied with the use of a nylon wool column and monoclonal antibodies. Peripheral blood lymphocytes (P.B.L.) from the patients (82 malignant gliomas, 65 metastatic brain tumors) were tested for their ability to inhibit lymphocytoblastogenesis, and reacted with monoclonal anti Leu 1, 2a and 3a antibodies to identify the subsets of T lymphocytes. Depression of the lymphocytoblastogenesis was detected significantly by the patients' P.B.L. passed through the nylon-wool column, but not detected by that adhering to the column. This suppressor cell activity was shown to do its work over the barrier of major histocompatibility complex, and seemed to be associated with Con. A-induced suppressor cell activity. Especially, in the patients with malignant gliomas, the suppressor T cells seemed to be induced by tumor cells, and mediate the noted immunodepression. Furthermore, analysis of T cell subsets using monoclonal antibodies showed that the suppressor cell activity in the patients with malignant gliomas seemed to be closely correlated with Leu 2a+ cells, and the Leu 3a+/Leu 2a+ ratio decreased with tumor loads suggesting that the suppressor T cells are more dominant than the helper T cells. These immunological studies help to advance therapeutic protocols of the patients, because suppressor cells may be related to the escape mechanism of malignant brain tumors.

Topics: Antibodies, Monoclonal; Brain Neoplasms; Concanavalin A; Female; Glioma; Humans; Immune Tolerance; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes

Topics: Adolescent; Adult; Brain Neoplasms; Child; Concanavalin A; Dose-Response Relationship, Drug; Female; Glioma; Humans; Male; Middle Aged; T-Lymphocytes, Regulatory

Peanut lectin (PNL), Concanavalin A (Con A) and Ulex europaeus lectin I (Ulex) were chosen to map their binding sites in different regions of formalin fixed and paraffin embedded human central nervous system tissue and pituitary gland tissues. An extended PaP method was used for PNL and Ulex, whereas a direct peroxidase technique was employed for Con A. In astrocytes, the cytoplasm as well as the delicate processes were stained by PNL and Con A; the most conspicuous binding of PNL was seen in the ependymal cells and on the surface of plexus epithelial cells; in the anterior part of the pituitary gland a selective population was PNL positive. Intracytoplasmic Con A acceptors could be demonstrated in neurons, in ependymal cells, and in plexus epithelial cells. Intracytoplasmic Con A receptors were finely granular in astrocytes, oligodendrocytes, and in some cells in the pituitary gland. Ulex binding was restricted to the vascular endothelial cells and a selective population of cells in the pituitary gland. Our results suggest that lectins may be good tools for the evaluation of their respective target cells in the central nervous system and in the pituitary gland.

Topics: Arachis; Binding Sites; Brain Neoplasms; Concanavalin A; Cytoplasm; Humans; Immunoenzyme Techniques; Lectins; Nerve Tissue; Pituitary Gland; Plant Lectins; Protein Binding; Receptors, Mitogen

Using a lectin-peroxidase method, Concanavalin A binding was examined on formalin-fixed paraffin-embedded biopsy specimens (n = 143) of the most frequent central nervous system tumours. The brain tumours included oligodendrogliomas, astrocytomas, glioblastomas, ependymomas, neurinomas, meningiomas, medulloblastomas and plexus papillomas. In oligodendroglioma cells, only a weak granular intracytoplasmic staining was observed. The astrocytomas showed a strong reaction in fibrillary astrocytes and in tumour areas undergoing small cystic degeneration. Staining of protoplasmic astrocytes was weaker; pilocytic astrocytes demonstrated poor perinuclear staining. Intracytoplasmic Con A binding in gemistocytic astrocytes was distinct but inconstant and rather diffuse. In the glioblastomas the lymphocyte-like small astrocytes were negative. Giant multinucleated astrocytes stained strongly. In ependymomas no or at most a weak perinuclear reaction was observed, whereas the acceptor density was as high as in the normal ependymocytes in areas where the tumour was capable of producing organotypical structures. Plexus papillomas showed a strong intracytoplasmic staining comparable to the normal plexus epithelial cell. This feature was preserved in the malignant variants. In general, meningiomas and neurinomas were negative. Xanthomatous-degenerated meningioma cells, however, showed a distinct to strong intracytoplasmic staining. This feature was characteristic for the xanthomatous subtype of meningiomas. Granular cells with strong intracytoplasmic Con A staining often occurred at the border of fibrillary to reticular differentiated areas of neurinomas. Medulloblastomas were completely negative. Our results indicate that Con A binding to human brain tumours is specific and rather cytotypical than histotypical . The Con A acceptor density is probably related to the grade of differentiation. Lectin mapping of tumours leads to cytotypical binding patterns which may contribute to the differential diagnosis of neoplasias.

Topics: Astrocytoma; Brain; Brain Neoplasms; Cerebellar Neoplasms; Concanavalin A; Ependymoma; Glioma; Humans; Immunoenzyme Techniques; Medulloblastoma; Meningeal Neoplasms; Meningioma; Neurilemmoma; Oligodendroglioma; Papilloma; Receptors, Concanavalin A

A case of meningioma arising from the right sphenoidal ridge is presented. Histologically, the tumour was composed of whorls of meningotheliomatous cells and many tumour cells containing intracellular inclusions were PAS positive, but diastase and neuraminidase resistant. The inclusions were named pseudopsammoma bodies by Kepes in 1961. The meningioma with pseudopsammoma bodies are a very rare entity and have been described in only 7 previous reports. We had an opportunity to examine one case of a meningioma with pseudopsammoma bodies. Electron microscopically, these substances were located in the intracellular spaces lined by microvilli. In earlier reports, the substances were said to be secretory products and a possibility of meningioma cell differentiation to secretory cell was postulated. Using the Concanavalin A staining method, the results of our present study strongly support this opinion.

Topics: Adult; Brain Neoplasms; Concanavalin A; Female; Histocytochemistry; Horseradish Peroxidase; Humans; Meningioma

Peripheral blood lymphocytes obtained from patients with primary intracranial tumors were assessed for the presence of Concanavalin-A-activated, glass-adherent, and spontaneous, nonspecific suppressor cells. Additionally, the effect of indomethacin on phytohemagglutinin (PHA)-induced blastogenesis was determined. No significant differences in cellular suppressor mechanisms in these patients and normal controls were observed. However, shifts in lymphocyte populations were demonstrable when cells were separated according to quantification of PHA-L surface binding sites by flow microfluorometry. Therefore, although impaired cellular responsiveness in patients with cerebral neoplasms does not appear to be due to alterations in suppressor-cell function, changes in lymphocyte subpopulations occur that may be induced as an immunobiological consequence of primary central nervous system neoplasia and contribute to suppressed host immunocompetence.

Topics: Adult; Aged; Brain Neoplasms; Cell Separation; Concanavalin A; Female; Flow Cytometry; Humans; Immunocompetence; In Vitro Techniques; Indomethacin; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Phytohemagglutinins; Receptors, Mitogen; T-Lymphocytes, Regulatory

The mitogenic responsiveness of spleen cells obtained from avian sarcoma virus-inoculated Fischer 344 rats was studied. Sixty % of the rats had astrocytomas, 13% had sarcomas, 7% had mixed gliosarcomas, and 20% had no evidence of tumors. Only spleen cells from rats bearing astrocytomas had significantly diminished responses to phytohemagglutinin and concanavalin A (Con A) when compared to control responses. The decreased responsiveness observed with phytohemagglutinin was limited to the optimal concentration range (10 and 20 microgram) while a broader concentration of Con A (0.01 to 50 microgram) induced significant suppression. Moreover, a more profound immunosuppression was observed with Con A. The results also demonstrated that spleen cells from rats with the largest astrocytomas exhibited the greatest suppression. From the results of this study, it appears the avian sarcoma virus-induced astrocytoma in rats is an immunological parallel of the human disease based on the loss of general immunological competence as assessed by responsiveness of lymphocytes to phytohemagglutinin and Con A.

Topics: Alpharetrovirus; Animals; Astrocytoma; Brain Neoplasms; Concanavalin A; Glioma; Immunity; Lectins; Lymphocyte Activation; Male; Neoplasms, Experimental; Rats; Rats, Inbred F344; Sarcoma, Avian; Spleen

Topics: Astrocytoma; Brain Neoplasms; Concanavalin A; Glioma; Humans; Lectins; Lymphocyte Activation

The immunocompetence of patients with glioblastomas, but not patients with astrocytomas, is altered. In vitro testing demonstrates an inhibitory factor in the serum of patients with glioblastomas which impairs lymphocytic responsiveness. The degree of this impairment appears important in relation to the clinical course.

Topics: Adult; Aged; Astrocytoma; Brain Neoplasms; Concanavalin A; Female; Humans; Lectins; Lymphocyte Activation; Male; Middle Aged