Neuroepithelial Origin Research Articles

Immunoreactivity of human MAb BT32/A6 with neuroepithelial tumors.

The present study was undertaken to determine the pattern of immunoreactivity of BT32/A6, a human IgM monoclonal antibody (MAb), with the following histological panels: 1) 30 human and non-human cell lines, 2) 32 normal human tissues, and 3) 28 tumors of central neuroepithelial origin (16 astrocytic; 11 non-astrocytic). Antibody BT32/A6 recognizes a surface and cytoplasmic antigen present on a variety of human tumor cell lines including gliomas, melanomas, neuroblastomas, and a few sarcomas. The antigen is present (at least focally) on 15/16 astrocytic tumor tissue sections (94%), and in some cases, on close to 100% of cells. All malignant cell types, including small anaplastic cells, giant cells, gemistocytic cells, and cells forming pseudopalisades were labeled by MAb BT32/A6. Non-astrocytic neuroepithelial tumors did not stain appreciably with MAb BT32/A6. There was weak immunoreactivity in a small subset of normal human tissues of epithelial and lymphoid origin, with the exception of adrenal cortex, which exhibited weak to moderate staining. All normal tissues of neuroectodermal and mesenchymal origin were unreactive. In conclusion, MAb BT32/A6 appears to be unique in that it recognizes a highly-expressed astrocytic tumor-associated antigen that is present on both low and high grade tumors. This makes it a strong candidate for further studies aimed at establishing its usefulness in the treatment of human astrocytic tumors.

The level of MnSOD is directly correlated with grade of brain tumours of neuroepithelial origin.

The oxy-radical scavenger enzyme manganese superoxide dismutase (MnSOD) may act in the capacity of a tumour-suppressor gene. To address the issue of its role in tumour transformation and progression in vivo, we evaluated the content of this enzyme in 33 brain tumours of neuroepithelial origin with different degrees of differentiation (WHO grade II-IV) by means of Western blot and immunohistology. Our results show that immunoreactive MnSOD increases in a direct relationship with tumour grade and is therefore inversely correlated with differentiation. The increase in induced at a pretranscriptional level and is apparently specific to brain tumours of neuroepithelial origin. Approximately 30% of grade IV tumours display low levels of MnSOD content, and preoperative radiotherapy and brachytherapy result in low amounts of enzyme. Based upon these observations, we suggest that MnSOD cannot be considered a classical tumour-suppressor gene.

Lower Urinary Tract Disease in Cats—New Problems, New Paradigms

Companion animal diets may be related to prevention, pathogenesis and/or treatment of diseases of the lower urinary tract. For example, urolithiasis can be either diet induced or nutrient sensitive. One of the most interesting developments in veterinary urolithiasis research has been the recent change in the composition of stones recovered from cats. In 1984, 88% of stones analyzed by quantitative methods were > 70% struvite, whereas < 1% were calcium oxalate. In 1992, the percentage of struvite had dropped to 62, whereas the percentage of calcium oxalate had increased to 24. Another recent development in lower urinary tract disease of cats is the recognition that urolithiasis appears to be a minor cause of the signs of frequency, urgency and hematuria for which patients are presented. This suggests that diet may no longer be involved, or be involved in previously unrecognized ways, in many current cases of this disease. Some of these feline patients may have a disease similar to interstitial cystitis, a disease of humans that appears to be of neuroepithelial origin. Our laboratory has been studying this possibility recently, and many similarities between the two diseases have been found.

Cellular pattern of type-I insulin-like growth factor receptor gene expression during maturation of the rat brain: Comparison with insulin-like growth factors I and II

Insulin-like growth factors have a number of potent trophic effects on cultured neurat tissue and most if not all of these effects appear to be mediated by the type-I insulin-like growth factor receptor. In order to establish the identity of cell types expressing this receptor in the rat centrat nervous system during development and maturity, we have used in situ hybridization to map sites of type-I insulin-like growth factor receptor mRNA synthesis in the developing and adult rat brain. In order to identify possible local sources of peptide ligands for this receptor, we have also mapped the sites of insulin-like growth factors I and II mRNA synthesis in paratlel brain sections. From early development onward, there is a uniform and stable pattern of type-I insulin-like growth factor receptor gene expression in all neuro epithelial cell lineages, in which regional variations reflect primarily differences in cell density. In addition to this generatized pattern, during late postnatal development, high levels of type-I insulin-like growth factor receptor gene expression are found in specific sets of sensory and cerebellar projection neurons in conjunction with abundant insulin-like growth factor-I gene expression in these same neurons. While insulin-like growth factor-I expression is confined to the principal neurons in each system, receptor mRNA is also found in local interneurons. In the cerebrat cortex and hippocampal formation, type-I insulin-like growth factor receptor mRNA and insulin-like growth factor-I are concentrated in different cell populations: receptor mRNA is abundant in pyramidal cells in Ammon's horn, in granule cells in the dentate gyrus, and in pyramidal cells in lamina VI of the cerebrat cortex. Insulin-like growth factor-I mRNA is found in isolated medium- to large-sized cells which are rather irregularly distributed throughout the hippocampus and isocortex. In the hypothalamus, receptor mRNA is concentrated in the suprachi asmatic nucleus but is in low abundance elsewhere, including the median eminence, while insulin-like growth factor-I mRNA is not detected in this region at all. Type-I insulin-like growth factor receptor and insulin-like growth factor-II mRNAs are both abundant in choroid plexus, menínges and vascular sheaths from early development to maturity, but insulin-like growth factor-II mRNA is not detected in cells of neuroepithelial origin at any stage of development. This study provides evidence for two fundamentally different patterns of gene expression for the brain type-I insulin-like growth factor receptor. Firstly, there is a relatively stable and uniform level of receptor gene expression shared by all neuroepithelial lineages. This receptor distribution may be the target of circulating insulin-like growth factors, which are secreted into the bloodstream by the liver and into the cerebrospinal fluid by the choroid plexus, and subserve a very basic metabolic or trophic function. Secondly, superimposed upon this apparently constitutive pattern, during the course of postnatal differentiation, specific sets of neurons show high levels of type-I receptor gene expression in conjunction with local insulin-like growth factor-I expression. These findings suggest that there are specific local fields of paracrine and/or autocrine insulin-like growth factor-I action mediated by the type-I receptor in the brain parenchyma.

Rat glioma cell lines C6 and 9L synthesize type 1 collagen in vitro

Glial cell lines (C6, a glioma and 9L, a gliosarcoma) grown in vitro produce type 1 collagen which is detectable in the extracellular matrix by immunocytochemistry. Northern blot analysis using a cDNA specific for the proalpha2 (I) chain of procollagen indicates the presence of a single transcript with an apparent size of 4.8 kb in the C6 cell line, whereas two transcripts with apparent sizes of 5.8 and 4.8 kb are visualized in the 9L cells. The stimulatory effect of ascorbic acid on collagen production is detectable by a 20–27% increase in the concentration of hydroxyproline in the culture medium from the two glioma cell lines. Therefore these glioma cell lines provide a valuable model system for comparative investigations on the regulation of type 1 collagen synthesis by nonmesenchymal cells of neuroepithelial origin.

Establishment of a rhabdoid tumor cell line with a specific chromosomal abnormality, 46,XY,t(11;22)(p15.5;q11.23)

The malignant rhabdoid tumor is a rare, poorly understood tumor which occurs primarily in children. The kidney is a frequent primary site of origin, but the tumor has arisen in other mesodermally derived tissues as well. Controversy exists regarding the embryonic origin of the rhabdoid tumor and recent histopathologic studies suggest that it may be of neuroepithelial origin. Our immunohistochemical and electron micrographic studies support this theory. No consistent chromosome abnormalities have been reported in this tumor and no cell lines are available for study. We have established and characterized the first rhabdoid tumor cell line. It possesses a specific chromosomal abnormality, 46,XY,t(11;22)(p15.5;q11.23). The translocation may provide an important clue to the pathogenesis of the tumor as well as an opportunity for further study of the involved chromosome regions.

Gliomatosis cerebri: Diagnostisches Potential der MRT

Gliomatosis cerebri is a rare tumor of neuroepithelial origin in middle aged persons presented by deterioration of cognitive functions, psychomotor retardation and cerebral convulsions. MRI predominantly shows a bilateral and diffuse infiltration of midline adjacent brain structures including medulla. Areas with focal anaplasia occasionally reveal an accumulation of contrast media. The diffuse tumor manifestation requires a differentiation from encephalitis and demyelinating diseases with a similar distribution pattern of lesions. Three cases have been examined. In conclusion the performance of MRI including control and brain biopsy are indicated to establish an in vivo diagnosis.

Modulation of Human Neurite Outgrowth by Serine Proteases: A Comparison of the Interaction of Thrombin and Prothrombin with Glia-Derived Nexin.

Neurite outgrowth from cells of neuroepithelial origin is under the reciprocal control of thrombin and the thrombin inhibitor-glia-derived nexin (GDN). The neurite retraction activity of thrombin is blocked when GDN complexes with the enzyme and inhibits its proteolytic activity. However, we have previously shown that enzymically inactive proenzyme is also capable of inducing neurite retraction. We present evidence here to show that GDN does not bind to prothrombin in solution. When a mixture of prothrombin and GDN is subjected to either polyacrylamide gel electrophoresis or immunoprecipitation, a stable complex cannot be detected. This is in direct contrast to thrombin, which exhibits stable complexes with GDN under both conditions. At the cell surface, however, GDN is able to inhibit the biological activity of prothrombin. When a mixture of proenzyme and inhibitor is applied to previously differentiated transformed retinoblasts (Ad12 HER10), the ability of prothrombin to induce neurite retraction is blocked. Furthermore, following 1 h exposure to Ad12 HER10 cells, a solution of prothrombin was found to contain half the potential enzyme activity as detected by chromogenic assay. These results have been interpreted as evidence for the ability of neuronal cells to cleave prothrombin and subsequently release activated enzyme.

Primitive Neuroectodermal Tumor with Wilms' Tumor

Occurrence of embryonal kidney tumors in patients with primitive neuroectodermal tumors, so-called central nervous system-renal neoplasia has been reported. An infant who presented with masses in the right lateral ventricle and the cerebellar vermis is reported. Histological examination showed primitive neuroectodermal tumors. Further investigation revealed tumors in the bilateral kidneys, which were removed subtotally and pathologically shown to be Wilms' tumors. The patient was then treated with anticancer drugs and irradiation. However, he developed lung metastases from the renal tumors and expired. At autopsy, a small tumor was found in the inferior horn of the left lateral ventricle. Histological finding showed a primitive neuroectodermal tumor. Also, bilateral large masses of recurrent Wilms' tumors, multiple metastases to the lungs and peritoneal dissemination were found. There is no evidence that this association is based on the selective neoplastic transformation of embryonal cells of similar histogenetic or cytogenetic origin. Several reports demonstrate the presence of embryonal cells in the nervous tissue which could imply a neuroepithelial origin for Wilms' tumors.

Symptomatic neuroepithelial (colloid) cysts of the third ventricle. A unique case report in nontwin brothers

Colloid cysts are relatively rare benign tumors comprising less than 2% of all intracranial mass lesions. However, since the advent of computed tomography of the head, these tumors are being recognized more frequently, occasionally before their symptomatic presentation. Much controversy remains as to the true cells of origin and pathogenesis of these cysts. Although a neuroepithelial origin has become increasingly accepted, Rathke cleft cysts, ectopic respiratory tissue, and other endodermal sources have been postulated. The first familial occurrence in middle-aged identical twin brothers was cited recently in the literature. Described here are the first reports of symptomatic colloid cysts in two nontwin brothers, lending further support to the potential for genetic expression of neuroepithelial cysts. Also included are preoperative computed axial tomographic images, histopathologic photomicrographs with case descriptions and comparisons, and suggestions to elucidate further the development and presentation of colloid cysts.

Pathology of Tumours of the Nervous System

Incidence pathogenesis and other general aspects experimental tumours of the nervous system tumours of central neuroepithelial origin tumours of specialized tissues of central neuroepithelial origin the growth of dissemination of central neuroepithelial tumours tumours of the meninges and related tissues tumours of the cranial, spinal and peripheral nerve sheaths nervous system involvement by lymphomas, histiocytoses and leukaemias tumours of vascular origin tumours and tumour-like lesions of maldevelopmental origin dysgenetic syndromes (phacomatoses) associated with tumours and hamartomas of the nervous system secondary tumours of the nervous system deformations and other structural changes produced by intercranial tumours effects of radiation and other forms of therapy on intracranial and spinal tumours and their surrounding tissues tumours of peripheral neuroblasts and ganglion cells paragangliomas.

Neuroepithelial small cell carcinoma of the vagina

We studied two patients with primary vaginal small cell carcinomas. Their tumors show histologic and ultrastructural neuroepithelial elements similar to those reported in the literature in the cervix and the lung. The clinical behavior of the tumors was aggressive in both patients. Ultrastructural study of small cell genital tract neoplasms is indicated to help classify this disease. Adjunctive therapy may be required for neoplasms of neuroepithelial origin.

Interferon inhibits the accumulation of glycerol phosphate dehydrogenase mRNA in oligodendrocytes and C6 cells

We investigated the effect of rat interferon-alpha/beta (IFN) on the expression of glycerol phosphate dehydrogenase (E.C.1.1.1.8; GPDH), in both C6 cells and pure cultures of oligodendrocytes. IFNs are naturally produced inhibitors of cell growth that can also affect differentiated cell functions. GPDH is a biochemical marker for oligodendrocytes and is known to be developmentally regulated and steroid inducible. GPDH activity is induced by hydrocortisone (HC) 3.5 fold in C6 cells and 5 fold in oligodendrocytes compared to untreated cultures. A pretreatment of these cells with 75 U/ml of rat IFN-alpha/beta resulted in an inhibition of the HC induction of GPDH enzymatic activity by 50% and 40% in C6 cells and oligodendrocytes respectively. We also found that IFN impaired the accumulation of GPDH mRNA in both cell types. These results demonstrate that IFNs are capable of modifying the cellular response to hormones in cells of neuroepithelial origin, and suggest the possibility that IFNs may be able to influence the development and function of the brain.

Colloid Cyst of the Fourth Ventricle: Diagnostic Problems and Pathogenic Considerations

ABSTRACT The authors report the case history of a patient with a colloid cyst of the 4th ventricle. The clinical history of slow intracranial hypertension, homogeneous hyperdensity with contrast enhancement on computed tomographic, scan, and the gelatinous aspect of the cyst at surgery are characteristic of colloid cysts. The diagnosis was made, however, only at the time of histological examination. A common neuroepithelial origin with 3rd ventricle cysts would be explained by similar embryological developments of the prosencephalic and the rhombencephalic roofs.

A neuroectoderm-associated ganglioside participates in fibronectin receptor-mediated adhesion of germinal cells to fibronectin

Previous studies with a rat neural cell line have shown that the D1.1 ganglioside, an O-acetylated derivative of GD 3, is involved in cellular adhesion to fibronectin. In vivo, D1.1 is present on germinal cells of the developing rat central nervous system, but not on postmitotic cells that migrate away from the germinal zones. These observations suggest that D1.1 could participate in adhesive interactions within germinal zones and that the loss of D1.1 could be involved in the decision to begin migration. In support of this hypothesis, immunofluorescence histochemistry shows that both fibronectin and fibronectin receptor are colocalized with D1.1 in the ventricular zones of the embryonic rat brain and in the external granule cell layer of the postnatal cerebellum. Dishes coated with monoclonal antibody against D1.1 were used to isolate D1.1-positive germinal cells from Embryonic Day 14 cerebrum and from Postnatal Day 6 cerebellum. These cells are able to adhere to fibronectin-coated dishes by a mechanism that is inhibitable by a synthetic hexapeptide containing the arg-gly-asp cell recognition sequence of fibronectin. Adhesion is also partially inhibited by antibody against fibronectin receptor and is slowed by anti-D1.1 antibody, implicating both the receptor and the ganglioside in the adhesion process. During 3 days in culture these D1.1-positive, fibronectin receptor-positive cells exhibit a neuronal phenotype, as judged by morphology and staining with tetanus toxin. This further confirms the neuroepithelial origin of the cells. The cells do not synthesize detectable amounts of fibronectin, thus leaving unidentified the source of the fibronectin seen in the germinal zones in tissue sections. Immunoprecipitation experiments show that the fibronectin receptors present on these cells are heterodimers. Under nonreducing conditions, the immunoprecipitates contain an α-subunit of 150–160 kDa and a β-subunit of 115–125 kDa.

Purification of a serum factor which reverses dibutyrl cAMP induced differentiation

We have previously shown [Grabham et al. (1988) Expt. Eye Res. 47, 123–133] that the adenovirus 12 transformed human retinoblast cell line (Ad 12 HER 10), like a number of other cell types of neuroepithelial origin, can be induced to differentiate in response to exposure to dibutyryl cAMP, and that this differentiation can be rapidly reversed by foetal calf serum. We present data here to show that a single protein, which we have termed differentiation reversal factor (DRF) and have isolated from serum, is responsible for this activity. Following reversal by DRF the growth rate of these cells was shown to be stimulated in serum-free medium. Using ammonium sulphate fractionation, gel filtration chromatography (Ultrogel AcA44), anion exchange chromatography (DEAE cellulose) and preparative gel electrophoresis, DRF has been purified to homogeneity, as judged by polyacrylamide gel electrophoresis in the presence and absence of SDS. The protein has a mol. wt of 72,000 and appears to exist in vivo as a monomer. The concentration of DRF in serum is in the range 100–500 μg/ml and is capable of reversing cAMP-induced differentiation of various primary human neuroepithelial cells at physiological concentrations.

Peptide hormone production associated with small cell lung cancer.

Small cell lung cancer (SCLC) is frequently associated with polypeptide hormone production, and a number of paraneoplastic syndromes have been reported. The neoplasia is thought to originate in the so-called Kulchitsky or K cells, small granular basal cells with endocrine properties found in the tracheobronchial mucosa (Tischler 1978). These K cells and the related SCLC and carcinoid tumor cells share APUD cell characteristics, such as cytoplasmic and membrane-bound dense core (“neurosecretory”) granules, amine precursor uptake and decarboxylation of precursors to biogenic amines by l-dopa decarboxylase, and storage of amines and polypeptide products in the neurosecretory granules (Pearse 1969). It has therefore been suggested that APUD cells and their tumors have a neuroepithelial origin different from the endodermal origin of the rest of the respiratory mucosa and its related neoplasia, such as squamous cell carcinoma and adenocarcinoma (Pearse 1969). However, morphological findings of foci of squamous carcinoma and adenocarcinoma in SCLC (Carney et al. 1982), the simultaneous appearance of histologically different multiple lung cancer (Gazdar et al. 1981), and ultrastructural evidence that SCLC cells may undergo squamous cell metaplasia (Mackay et al. 1977) favor the hypothesis that all bronchial mucosa cells and the tumors arising from them have a common origin. Although polypeptide hormone production is more frequently associated with SCLC, other types of lung cancer with non-APUD cell characteristics frequently show hormone secretion (Rose 1979). Furthermore, hormonal peptides are produced by a number of other solid tumors, by lymphomas, and by different types of leukemia (Pflüger et al. 1981, 1982).

Cerebellar neoplasm of mixed mesenchymal and neuroepithelial origin

A 3 1/2-year-old boy had a neoplasm of mixed mesenchymal and neuroepithelial origin in the cerebellar vermis. The tumor was composed of rhabdomyosarcoma and medulloblastoma. There was additional differentiation within the neuroepithelium, including neoplastic neurons, neuroblasts, astroglia, oligodendroglia, ependymal cells as well as foci of glioblastomatous transformation. It is suggested that this combined tumor arose from the neural crest or combined neural crest and neural tube. The rhabdomyosarcoma could have arisen from the mesenchymal portion of the neural crest, and the medulloblastoma from the neuroectodermal part of the neural crest or from the neural tube itself. The two tumor types formed a neoplasm of mixed mesenchymal and neuroepithelial origin.

Neuronal and astrocytic differentiation in human neuroepithelial neoplasms. An immunohistochemical study.

Neuroepithelial neoplasms of childhood were examined immunohistochemically using antibodies against a neurofilament polypeptide and glial fibrillary acidic protein. Ninety-one cases, including 11 controls, were examined. Positively reacting cells, indicating neuronal and glial differentiation, were found in 59 of the 80 tumors. The study supports a neuroepithelial origin for medulloblastomas, central neuroblastomas, and primitive neuroectodermal tumors of childhood. The results also indicate that only a small number of the tumor cells differentiate along either neuronal or glial cell lines.

Human converting enzyme.

Angiotensin I converting enzyme (kininase II, peptidyl dipeptidase, ACE) was purified by reverse immunoadsorption from a membrane fraction of the human kidney. ACE is very likely a transmembrane peptidase. Treatment of the membrane-bound enzyme with trypsin releases a low mol. wt. fragment (greater than 10,000), which is probably the anchor peptide inserted into the plasma membrane. Antibody to ACE was used to localize it in the CNS where it is bound to plasma membrane of neuroepithelial cells in structures such as the globus pallidus or substantia nigra. Radioimmunoassay indicated that ACEs of endothelial, epithelial and neuroepithelial origin are immunologically identical. Direct radioimmunoassay also showed that there is a strong negative correlation between plasma enzyme level and pulmonary diffusing capacity of sarcoid patients. Finally, in addition to various peptides, homogeneous human ACE cleaves fluorogenic substrates where the C-terminal amino acid is replaced with nitrobenzylamine.