Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Variant sublines of the murine lymphosarcoma RAW117 have been derived by sequential cycles of intravenous inoculation of cells and harvesting of solid liver tumors in syngeneic BALB/c mice [Brunson K. W. & Nicolson, G. L. (1978) J. Natl. Cancer Inst. 61, 1499-1503] and also by sequential removal of lectin-reactive cells via repeated adsorption on immobilized-lectins [Reading, C. L. Belloni, P. N. & Nicolson, G. L. (1980) J. Natl. Cancer Inst. 64, 1241-1249]. These cell sublines and their clones were analyzed for abilities to form gross liver tumor metastases after injection intravenously or subcutaneously into syngeneic mice, and this response was related to certain cell surface properties including quantities of viral antigens and lectin-binding sites, exposure of specific cell surface proteins, and quantities of cell surface glycoproteins visualized in gels with 125I-labeled lectins or antibodies. Consistent differences were obtained between RAW117 sublines of low and high malignancy with respect to the amounts or exposures of cell surface glycoprotein components of Mr approximately 70,000 or 69,000 and 71,000, depending on the gel system. Competition radioimmunoassays for RNA tumor virus antigens in the RAW117 lines and clones indicated the presence of Moloney murine leukemic virus antigens gp70, p30, and p12. Enhanced malignancy and metastasis to liver was accompanied by decreases in the cellular contents of viral antigens and loss of gp70 cell surface exposure. Analysis of several clones obtained from sublines selected in vivo and in vitro for high or low malignancy confirmed the inverse relationship between metastasis and expression of gp70 in this system.
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PMID:Malignancies of metastatic murine lymphosarcoma cell lines and clones correlate with decreased cell surface display of RNA tumor virus envelope glycoprotein gp70. 693 25

Hyaluronan-binding sites were demonstrated on the cell surface of three malignant mesothelioma cell lines derived from human tumors using either [3H]hyaluronan or fluorescein-tagged hyaluronan. No hyaluronan-binding activity was observed on normal human mesothelial cells. The absence of hyaluronan receptors on normal human mesothelial cells was not due to a down-regulation by endogenously synthesized hyaluronan, since no binding sites appeared when the cells were cultured under conditions known to suppress hyaluronan synthesis (in starvation medium containing either hydrocortisone or n-butyrate) or to degrade endogenously synthesized hyaluronan (in the presence of Streptomyces or testicular hyaluronidase). The binding of [3H]hyaluronan on mesothelioma cells could be partially inhibited by prior incubation of the cells with trypsin, indicating that the hyaluronan-binding site is a protein. The binding sites on human malignant mesothelioma cells were shown to be saturable with about 54,000 hyaluronan molecules (M(r) 1.4 x 10(6)) bound per cell with a Kd of 0.3 x 10(-9) M. The binding was specific for hyaluronan inasmuch as a number of other macromolecules gave negligible inhibition of the binding. High molecular weight preparations of hyaluronan inhibited the binding more effectively than low molecular weight preparations; hyaluronan oligosaccharides down to a length of six monosaccharide units showed competing activity. The hyaluronan receptor appeared to be related to CD44 (a cell surface glycoprotein previously suggested to function as a hyaluronan receptor) since Hermes-1 monoclonal antibodies which inhibit the binding of hyaluronan to CD44 blocked a major part of the binding of hyaluronan to the mesothelioma cells. However, there was no strict correlation between the hyaluronan-binding activity on the mesothelioma cell lines tested and the levels of CD44 molecules on their cell surface, suggesting that only a subfraction of the CD44 molecules bound hyaluronan or that other hyaluronan-binding proteins also exist on those cells. The presence of hyaluronan receptors on mesothelioma cells, but not on their normal counterparts, may be of importance for the migration of the transformed cells in hyaluronan-enriched matrices and for their ability to form metastases.
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PMID:Hyaluronan receptors are expressed on human malignant mesothelioma cells but not on normal mesothelial cells. 751 23

Biliary glycoprotein (BGP), a member of the carcinoembryonic antigen gene family, is a cell surface glycoprotein that has both a transmembrane domain and a cytoplasmic domain. BGPs consist of at least four isoforms (BGPa, b, c, and d) and function in vitro as Ca(2+)-dependent homotypic intercellular adhesion molecules. The mRNA expression of BGP gene was investigated in specimens of primary and metastatic cancer tissues from 15 patients with primary lung cancer (six squamous cell carcinomas, five adenocarcinomas, and four small cell carcinomas). The specimens were also compared with normal adjacent tissues of the same individuals with squamous cell carcinoma. BGP mRNA expression was increased in carcinomatous tissues of the primary site, especially in squamous cell carcinoma, but was not detected in adjacent normal tissues by Northern blot analysis or in situ hybridization. Interestingly, BGP mRNA expression was apparently decreased in metastatic lesions compared with the primary site in the six individuals with squamous cell carcinoma. Furthermore, a loss of BGPa isoform was observed by reverse transcriptase-polymerase chain reaction in four of six patients with squamous cell carcinoma. These results suggest that the reduction of BGP expression may play an important role in the process of metastasis through decreasing adhesive interactions with surrounding cells, especially in squamous cell carcinoma.
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PMID:Biliary glycoprotein mRNA expression is increased in primary lung cancer, especially in squamous cell carcinoma. 804 82

CD44 is a cell surface glycoprotein which has been suggested to be associated with aggressive histological features in breast cancer (BC). It has also been implicated in conferring metastatic potential to rat carcinoma cells. The aim of this study was to determine the potential value of CD44 as a prognostic/metastatic marker in BC by means of immunohistochemistry. The expression of the CD44 glycoprotein was investigated in tumours from 52 untreated female patients with BC, using the monoclonal antibody A3D8. 10 samples of normal breast tissue were randomly obtained and also investigated with respect to CD44 expression. DNA ploidy, the S-phase fraction (SPF) and oestrogen-(OR) and progesterone-receptor (PgR) contents in the tumours were determined and together with the prognostic markers of age, tumour size, tumour grade and lymph node status, correlated with CD44 expression in BC. Also, the distribution of CD44 tumour cell expression was compared with expression of the permeability drug resistance glycoprotein (P-gp) in this material. Expression of CD44 on carcinoma cells was observed in 21/52 cases (40%). Capillary endothelial reactivity of the tumours occurred in 42 cases (80%). Non-neoplastic epithelial breast tissue was positive in 2/10 (20%) samples and capillary vessels in 7/10 (70%). Carcinoma CD44 cell expression was not associated with age, tumour size, tumour grade, DNA ploidy, SPF, hormone-receptor contents or lymph node metastases. There was a statistical correlation between CD44 and P-gp expression in breast carcinoma cells which may suggest a connection between adhesion molecules and drug resistance. These findings do not support an association between CD44 expression and adverse prognostic features or lymph node metastases in BC. Capillary CD44 staining was a common feature in BC. There appeared to be an upward regulation in CD44 expression in BC compared with the normal breast tissue.
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PMID:Expression of the CD44 glycoprotein (lymphocyte-homing receptor) in untreated human breast cancer and its relationship to prognostic markers. 866 66

Cell adhesion to and migration through extracellular matrices (ECM) are critical events in tumor invasion and metastasis. Previous work by us had demonstrated that signaling of epidermal growth factor receptor (EGFR) confers an oncogenic phenotype on NR6 cells and that these cells when transfected with holo EGFR demonstrate greater motility and invasiveness than cells carrying a carboxy-terminal truncated EGFR. Recently, a cell surface glycoprotein, CD44, has been implicated in cell-ECM adhesion involved in tumor cell migration, signal transduction, and metastasis. We investigated whether EGF regulates cellular interactions with ECM components, and in particular, hyaluronate, by modulating CD44 expression. In vitro cell attachment assays on hyaluronate-coated plates demonstrated similar basal level of binding (approximately 33%) for murine NR6 parental cells devoid of endogenous EGFR (P) or expressing wild-type EGFR (WT), while a time-dependent increase in binding was observed in WT cells stimulated with EGF. Additionally, utilizing monoclonal antibody blocking assays, CD44, but not EGFR, was shown to be directly involved in this attachment. Both WT and P cells possessed equivalent 95 kDa bands on immunoblots, corresponding to CD44. The existence of CD44 mRNA was verified by RT-PCR using synthetic oligonucleotides in which a 1.1 kb cDNA was detected in both cell lines and confirmed by DNA sequencing. After 24-h exposure to exogenous EGF, an increase in CD44 protein and mRNA expression was found in WT cells, but not in P cells, supporting the contention that a functional EGFR signaling pathway is required for CD44 regulation. Thus, EGF stimulates cell binding to hyaluronate in vitro by regulating CD44 expression.
Clin Exp Metastasis 1996 May
PMID:Epidermal growth factor modulates cell attachment to hyaluronic acid by the cell surface glycoprotein CD44. 867 81

Cutaneous small blue cell tumors are relatively uncommon and include primary lesions of either adnexal or neuroendocrine differentiation, as well as metastatic disease. Extraosseous Ewing's sarcoma/malignant primitive neuroectodermal tumor (MPNET) rarely may occur as a primary, superficially based neoplasm in children and young adults. We describe a series of five cases of Ewing's sarcoma/malignant primitive neuroectodermal tumor occurring as a primary cutaneous malignancy supported diagnostically both by immunohistochemical stains and fluorescence in situ hybridization (FISH). All five cases occurred as a solitary dermal nodule and were located in the lower extremities (3 cases), the axilla (1 case), and the flank (1 case). Three of the cases were clinically polypoid. Four of the five patients were female, and age at presentation ranged form 8 to 50 years of age (median, 18 years). All five tumors consisted of nodular proliferations of monomorphous, small blue cells with round, vesicular nuclei, and scant to moderate cytoplasm that were uniformly immunoreactive for the CD99 cell surface glycoprotein in a characteristic membranous pattern. Fluorescence in situ hybridization analysis of paraffin-embedded tissue revealed that three of four tumors were positive for a chromosomal translocation involving the EWS locus at 22q12, seen in more than 90% of cases of Ewing's sarcoma/malignant primitive neuroectodermal tumor. One case was not analyzable. All five patients were treated using local excision, and two patients additionally received postoperative chemotherapy and radiotherapy. Clinical follow-up is available in three cases (median duration, 33 months) and to date none has shown evidence of either local recurrence or metastasis. Because similar cases reported in the literature have likewise had favorable clinical courses after excision, primary cutaneous Ewing's sarcoma/malignant primitive neuroectodermal tumor may represent a clinically favorable subset of this otherwise highly aggressive neoplasm.
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PMID:Primary cutaneous Ewing's sarcoma: immunophenotypic and molecular cytogenetic evaluation of five cases. 950 Jul 72

Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein that is expressed by prostate epithelial cells. PSMA-specific monoclonal antibodies have been utilized to characterize the biologic function and in vivo biodistribution of PSMA. PSMA is an attractive target protein for monoclonal antibody directed imaging or therapeutics for prostate cancer since its expression is relatively restricted to prostate epithelial cells and is over-expressed in prostate cancer, including in advanced stages. Currently, clinical usage of PSMA specific monoclonal antibodies has been limited to diagnostic immunohistochemistry and imaging of patients with prostate cancer. Novel applications for these antibodies will be discussed.
Cancer Metastasis Rev 1999
PMID:Prostate-specific membrane antigen (PSMA)-specific monoclonal antibodies in the treatment of prostate and other cancers. 1085 91

The OX-40 receptor (OX-40R) is a cell surface glycoprotein of the tumor necrosis factor receptor family that is expressed primarily on activated CD4 T cells. Engagement of OX-40R by the OX-40 ligand (OX-40L) is known to costimulate the production of cytokines by activated T lymphocytes and to rescue effector T cells from activation-induced cell death. It was previously reported that in vivo ligation of OX-40R by administration of OX-40L:immunoglobulin fusion protein or OX-40R monoclonal antibody (mAb) resulted in a significant prolongation of survival of tumor-bearing mice in four histologically distinct solid tumors. In this study, we demonstrate that the therapeutic efficacy of OX-40R mAb was influenced by the tumor burden, the intrinsic immunogenicity of the tumor as well as by the histological site of tumor growth. Whereas subdermal and intracranial growth of weakly immunogenic MCA 203 and MCA 205 sarcomas and GL261 glioma were susceptible to the mAb treatment, established pulmonary MCA 205 metastases were refractory to the same regimen of treatment. Furthermore, the mAb administration had no impact on the growth of the poorly immunogenic B16/D5 mela noma. Tumor regression mediated by OX-40R mAb was dependent on the participation of both CD4 and CD8 T cells and as a result of tumor rejection, a long-term tumor-specific immunity was established. Analysis of tumor-infiltrating T cells revealed the presence of a far greater number of OX-40R+ T cells of both CD4 and CD8 phenotypes in the intracranial immunogenic GL261 glioma than that in the poorly immunogenic B16/D5 melanoma. These results suggest that ligation of OX-40R on activated T cells in situ in the tumor may provide a necessary costimulatory signal to augment immune responses leading to tumor regression and immunological memory.
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PMID:Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. 1103 96

Autocrine motility factor receptor (AMFR) is a cell surface glycoprotein of 78000 molecular weight (gp78), regulating cell motility signaling in vitro and metastasis in vivo. To test whether AMFR could be a common mediator of transformation and oncogenic itself, we transfected NIH3T3 fibroblast cells with expression vectors carrying the full-length cDNA for mouse AMFR and evaluated the effects of increased AMFR on transforming potential. The cells stably expressing high levels of AMFR as a result of transfection displayed a complete morphological change and acquired the ability to grow even in low serum. Furthermore, they were anchorage-independent for growth in soft agar and more motile in phagokinetic track assay. Interestingly, the enhanced expression of AMFR produced tumors in nude mice. Our findings provide a direct evidence that overexpression of the AMFR is associated with the acquisition of a transformation phenotype.
Clin Exp Metastasis 2003
PMID:Overexpression of autocrine motility factor receptor (AMFR) in NIH3T3 fibroblasts induces cell transformation. 1265 Jun 7

Neuroendocrine carcinomas of the uterine cervix are rare tumors with early metastases, highly aggressive clinical behavior, and poor clinical outcome. Several adhesion molecules like cadherins have been tested in an attempt to explain their unique characteristics. Cluster differentiation 44 (CD44) is a widely expressed cell surface glycoprotein that serves as an adhesion molecule in cell-to-substrate and cell-to-cell interaction. We have examined the expression of the standard CD44 (CD44s) by immunohistochemical stains in the paraffin-embedded cervical neoplasm tissue of 17 cases of primary cervical neuroendocrine carcinoma, 28 cases of cervical adenocarcinoma, and 50 cases of cervical squamous cell carcinoma. Loss of CD44s expression was found in 16 of 17 neuroendocrine carcinomas, 14 of 28 adenocarcinomas, and three of 50 squamous cell carcinomas. The differences were statistically significant. We also examined immunohistochemically the expression of the BRG-1 subunit of the SWI-SNF complex, which has been reported to regulate the expression of CD44 in all cases. Loss of BRG-1 expression was observed in 12/16, 6/14, and 1/3 CD44s-negative neuroendocrine carcinomas, adenocarcinomas, and squamous cell carcinomas, respectively. This study suggests that loss of the CD44s molecule may imply special biological behaviors of cervical neuroendocrine carcinomas, and loss of expression of BRG-1 may contribute to this.
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PMID:Downregulation of BRG-1 repressed expression of CD44s in cervical neuroendocrine carcinoma and adenocarcinoma. 1699 64


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