Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The monoclonal antibody 5.1 H11 recognizes an antigen on human fetal muscle and on rhabdomyosarcoma cell lines and xenografts that has been shown to be homologous to the neural cell adhesion molecule. To evaluate its range of expression, we used immunoperoxidase staining of fresh frozen-tissue sections to determine monoclonal antibody 5.1 H11 reactivity in normal and neoplastic tissue. Among normal tissue specimens, intense antibody staining was seen in brain and peripheral nerve, and weaker staining in ganglionic elements of colon. In addition to 26 of 29 rhabdomyosarcoma specimens, 5.1 H11 antibody showed reactivity to 9 of 10 Wilms' tumors, 6 of 6 neural tumors, and 4 of 4 gliomas, and with single specimens of ectomesenchymoma, clear-cell sarcoma of kidney, undifferentiated sarcoma of liver, ovarian fibroma, and neurofibroma. We conclude that the monoclonal antibody 5.1 H11 recognizes an antigen present not only on fetal muscle but on normal brain and nerve as well. In addition to rhabdomyosarcoma, a variety of other tumors, most of which have been previously shown to express neural cell adhesion molecule, also appear to express the antigen recognized by 5.1 H11. Our results thus offer additional confirmatory evidence that an epitope of neural cell adhesion molecule is the antigen for 5.1 H11.
 ...
PMID:Expression of the 5.1 H11 antigen, a fetal muscle surface antigen, in normal and neoplastic tissue. 218 73

The distribution of the neural cell adhesion molecule (N-CAM; CD56) was studied immunohistochemically in acetone-fixed frozen sections of 83 soft tissue tumors and selected normal mesenchymal tissue using Leu-19 monoclonal antibody and avidin-biotin peroxidase immunostaining. Positive N-CAM immunostaining was found in gastrointestinal and uterine cells but not in vascular smooth muscle cells. Normal skeletal muscle was negative, but atrophic muscle fibers within tumors were positive. Strong and consistent immunoreactivity was seen in nerves, pheochromocytoma, malignant schwannoma, and spindle cells, but not in epithelial-like cells of synovial sarcoma, hemangiopericytoma, benign leiomyoma, and rhabdomyosarcoma. Variable staining was seen in benign schwannoma and malignant fibrous histiocytoma. Limited, usually focal N-CAM immunoreactivity was seen in desmoid tumor, dermatofibrosarcoma, and leiomyosarcoma. Although the N-CAM is consistently seen in neural tumors, it is not cell lineage specific. Changes on malignant transformation (comparing corresponding benign and malignant lesions) do not show any consistent pattern. Rather, there is neoexpression of the N-CAM in rhabdomyosarcoma, whereas there is loss of the N-CAM in leiomyosarcoma. Immunohistochemistry of the N-CAM can be a useful adjunct for characterization of soft tissue tumors, and its possible correlation with tumor behavior has to be examined in further studies.
 ...
PMID:Neural cell adhesion molecule distribution in soft tissue tumors. 767 94

The MSD1 region of neural cell adhesion molecule (NCAM) was originally described as being spliced into the 120-kDa isoform of NCAM isolated from muscle. The 105 bp region is inserted between exons 12 and 13 and actually consists of three separate exons, MSD1a, MSD1b and MSD1c of 15, 48, 42 bp, respectively. In addition, a further exons consisting of a single triplet has been designated MSD1d, making the full insert size 108 bp. As the MSD1 region was originally described as being selectively expressed in muscle tissue, we have investigated whether it is also present on tumours of rhabdoid origins and whether its presence can be used as the diagnostic marker to distinguish other small round cell tumours of childhood, such as neuroblastoma. Using a variety of human tumour cell lines, we demonstrated the presence of the MSD1 region on all rhabdomyosarcomas investigated. However, neuroblastoma cell lines only expressed subcompartments of the MSD1 region. The MSD1c exon was not spliced into the NCAM molecules isolated from any of the neuroblastoma cell lines investigated. On the basis of this finding, it appears that neuroblastoma and rhabdomyosarcoma can be distinguished by the expression of MSD1c mini-exon. Further studies are underway to attempt to define a monoclonal antibody that recognises the region, using mice immunised with synthetic peptides, and to confirm the finding using fresh biopsy material.
 ...
PMID:Tissue-specific expression of neural cell adhesion molecule (NCAM) may allow differential diagnosis of neuroblastoma from embryonal rhabdomyosarcoma. 783 18

The neural cell adhesion molecule (NCAM) plays an important role in normal development. Many variants of NCAM are generated through post-transcriptional and post-translational modifications. These variants are tissue-specific and their expression is developmentally regulated. NCAM is also re-expressed in a number of human tumours, including neuroblastoma, rhabdomyosarcoma, Wilms' tumour and Ewing's sarcoma. We have characterized the NCAM variants associated with rhabdomyosarcoma. Polysialylated NCAMs are present in this tumour and, after neuraminidase treatment, they resolve into 2 bands of 140 and 120 kDa. These data were corroborated by Northern-blot analysis where mRNA species of 6.7 and 5.5 kb are detected. These mRNA code for the 140- and 120-kDa NCAM proteins respectively. PCR analysis shows that the previously described VASE mini-exon is also present in NCAM found in rhabdomyosarcoma. The VASE mini-exon, spliced at exon 7-8 junctions, has previously been detected in neural and heart NCAM, as well as in NCAMs found in human small-cell lung carcinoma (SCLC). DNA sequencing confirmed that the VASE mini-exon in rhabdomyosarcoma is identical to that found in neuroblastoma and SCLC.
 ...
PMID:Vase mini-exon usage by NCAM is not restricted to tumours of neuroectodermal origin. 832 6

Many cancer cells show aberrant adhesion properties that likely contribute to tumorigenesis, invasion, and metastasis. Here, we examine three MyoD-expressing, rhabdomyosarcoma-derived human cell lines (RD, A-204, and HS 729) for their expression of the neural cell adhesion molecule (N-CAM), N-cadherin, and the cadherin-associated proteins, alpha-catenin, beta-catenin, and plakoglobin, using specific antibodies and immunoblotting and immunocytochemical methods. Normally, during the formation of skeletal muscle, both N-CAM and N-cadherin are expressed and participate in mediating myoblast adhesion accompanying cell fusion. RD cells express N-CAM, N-cadherin, and the cadherin-associated proteins; however, N-CAM is expressed as a highly sialylated isoform that functions poorly in promoting Ca(2+)-independent cell aggregation. HS 729 cells express N-cadherin and its associated intracellular proteins but have no detectable N-CAM. A-204 cells express no detectable N-CAM or N-cadherin but do express cadherin-associated proteins. Thus, all three rhabdomyosarcoma cell lines exhibit some abnormality in the expression of adhesion molecules known to participate in skeletal myogenesis; however, no common defect was observed that might be considered as a characteristic marker for rhabdomyosarcomas.
 ...
PMID:Rhabdomyosarcoma-derived cell lines exhibit aberrant expression of the cell-cell adhesion molecules N-CAM, N-cadherin, and cadherin-associated proteins. 839 2

Rhabdomyosarcoma (RMS) cells express the polysialylated (PSA) form of the neural cell adhesion molecule (NCAM). During embryogenesis, PSA-NCAM is widespread and dynamically regulates embryonal developing processes, whereas postnatally, PSA-NCAM becomes restricted to a few regions of neural plasticity and regenerating neural tissues. Recently, PSA-NCAM has been shown to be a diagnostic and prognostic marker in adult patients with small cell lung cancer and multiple myeloma, both PSA-NCAM-expressing tumors. In this study, we determined the amount of PSA-NCAM in tumor specimens of nine children with different histologic types and clinical stages of RMS immunohistochemically, using the polysialic acid-specific MAb 735. In seven children, serum levels were investigated by an immunoluminescence assay using the same MAb. Patients with extensive disease showed strong staining of the tumor specimens, whereas patients with limited stages or after chemotherapy had distinctly a lesser amount of PSA-NCAM or almost no staining. Simultaneously, the serum levels were very high (up to 9-fold) in patients with extensive disease, whereas patients with limited disease or after successful therapy had normal serum levels. We conclude that PSA-NCAM expression is high in tumor specimens and serum of patients with advanced stages of RMS and decreases during successful therapy. PSA-NCAM might therefore serve as a marker for diagnosis and monitoring childhood RMS.
 ...
PMID:Polysialylated neural cell adhesion molecule in childhood rhabdomyosarcoma. 943 26

The 2;13 chromosomal translocation in alveolar rhabdomyosarcoma generates the chimeric protein PAX3-FKHR, which is a powerful transcriptional activator. We hypothesize that PAX3-FKHR regulates downstream effector genes involved in rhabdomyosarcoma tumorigenesis. We evaluated alterations in expression of MET and neural cell adhesion molecule that were proposed previously as downstream targets of wild-type PAX3. We used a myogenic tumor cell culture system and rhabdomyosarcoma tumor specimens to assess candidate gene expression in relationship to various PAX3-FKHR expression levels. We demonstrate that the expression of MET, but not neural cell adhesion molecule, correlates significantly with PAX3-FKHR expression. These findings indicate that MET, which encodes a receptor involved in growth and motility signaling, is a downstream target of PAX3-FKHR in alveolar rhabdomyosarcoma.
 ...
PMID:Up-regulation of MET but not neural cell adhesion molecule expression by the PAX3-FKHR fusion protein in alveolar rhabdomyosarcoma. 972 57

Serum concentrations of polysialylated neural cell adhesion molecule (PSA-NCAM), a developmentally regulated form of the NCAM, have been recently described to be elevated in children with rhabdomyosarcoma and neuroblastoma, proving PSA-NCAM to be a tumor marker of diagnostic relevance to these malignancies. The present investigation was undertaken to define age-dependent reference intervals in normal children. Serum concentrations of polysialylated NCAM were determined in 366 children aged newborn to 17 y and in 18 adult patients by an immunoluminescence assay using the polysialic acid-specific MAb 735. Serum levels in newborn children were 51.7 kU/L (mean +/- 12.0 kU/L SD), whereas in adult patients they were 9.9 kU/L (mean +/- 3.5 kU/l SD). Assigning the patients to 14 different age groups, a gradual decay of PSA-NCAM serum concentrations was observed, and therefore, mean levels and empirical interpolated percentiles were determined for every age group. Applying specially fitted logistic functions, two different sigmoid graphs were obtained describing the age-dependent decrease of serum PSA-NCAM during the neonatal period and during childhood. The age at which the levels reach half the initial value was located at 3.1 d (mean +/- 2 d SE) and 14 y (mean +/- 1 y SE), respectively. There was no difference between male and female individuals. Repeated measurements revealed variations below 10%. For the first time, our study describes serum levels of PSA-NCAM in children of different age and their gradual decay until adulthood.
 ...
PMID:Polysialylated neural cell adhesion molecule serum levels in normal children. 985 27

Polysialic acid attached to the neural cell adhesion molecule (NCAM) is thought to play a critical role in development. NCAM in muscle tissue contains a muscle-specific domain (MSD) to which mucin type O-glycans are attached. In the present study, using the C2C12 myoblast system, we show that NCAM containing MSD is increasingly expressed on the cell surface as myotubes form. Polysialic acid is primarily attached to N-glycans of NCAM, and polysialylated NCAM is expressed on the outer surface of myotube bundles. By transfecting cDNAs encoding wild type and mutant forms of NCAM, we found that NCAM containing MSD facilitates myoblast fusion, and this effect is diminished by mutating O-glycosylation sites at MSD. By contrast, forced expression of polysialic acid in early differentiation stages reduces myotube formation and delays the expression of NCAM containing the MSD domain. Strikingly, inhibition of polysialic acid synthesis by antisense DNA approach induced differentiation in both human rhabdomyosarcoma cells, which overexpress polysialic acid, and C2C12 cells. These results indicate that polysialic acid and mucin type O-glycans on NCAM differentially regulate myoblast fusion, playing critical roles in muscle development.
 ...
PMID:Polysialic acid and mucin type o-glycans on the neural cell adhesion molecule differentially regulate myoblast fusion. 1367 64

Rhabdomyosarcoma is a muscle-derived malignant tumor mainly affecting children. The most frequent variant, embryonal rhabdomyosarcoma (ERMS) is characterized by overexpression of the transcription factor, PAX7 which prevents ERMS cells from exiting the cell cycle and terminally differentiating. However, a role for PAX7 in the invasive properties of ERMS cells has not been investigated in detail thus far. Here we show that ectopic expression of receptor for advanced glycation end-products (RAGE) in human ERMS cells results in the activation of a RAGE/myogenin axis which downregulates PAX7 by transcriptional and post-translational mechanisms, as in normal myoblasts, and reduces metastasis formation. High PAX7 sustains migration and invasiveness in ERMS cells by upregulating EPHA3 and EFNA1 and downregulating NCAM1 thus decreasing the neural cell adhesion molecule (NCAM)/polysialylated-NCAM ratio. Microarray gene expression analysis shows that compared with the RAGE(-ve) TE671/WT cells and similarly to primary human myoblasts, TE671/RAGE cells show upregulation of genes involved in muscle differentiation and cell adhesion, and downregulation of cell migration related and major histocompatibility complex class I genes. Our data reveal a link between PAX7 and metastasis occurrence in ERMSs, and support a role for the RAGE/myogenin axis in metastasis suppression. Thus, low RAGE expression in ERMS primary tumors may be predictive of metastatic behavior.
...
PMID:Defective RAGE activity in embryonal rhabdomyosarcoma cells results in high PAX7 levels that sustain migration and invasiveness. 2512 33


1