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)

The clinical presentation of cervical metastases in a young woman presenting with cervical lymphadenopathy is described. The clinical, histological, ultrastructural and immunological findings establishing the diagnosis of a renal primary tumour are seen. The significance of mixed tumour cell expression of antigens specific for the proximal tubule (CD10, DPP4 and aminopeptidase N) and of Tamm Horsfall protein, normally expressed on the thick ascending limb of loop of Henle and distal tubule, is discussed.
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PMID:Tamm Horsfall protein expression by a small renal cell carcinoma presenting with metastases. 196 77

Aminopeptidase N/CD13 is a Zn(2+)-dependent exoprotease present on the cell surface as a transmembrane protein. Our previous studies using aminopeptidase inhibitors and antibodies demonstrated that aminopeptidase N is involved in the degradation and invasion of the extracellular matrix (ECM) by metastatic tumor cells. In the present study we transfected human A375M melanoma cells with eukaryotic plasmid expression vectors that contained full length cDNA of aminopeptidase N/CD13 and examined their characteristics. The transfectants that expressed extremely high levels of aminopeptidase N/CD13 degraded type IV collagen and invaded ECM more actively than the parental and control vector-transfected cells. Furthermore, the aminopeptidase N/CD13-transfected A375M cells had significantly augmented lung colonizing potential in nude mice. The results show that the aminopeptidase N/CD13 plays an active role in degradation and invasion of ECM and may be involved in the molecular mechanisms of blood-borne metastasis.
Clin Exp Metastasis 1995 Sep
PMID:Human melanoma invasion and metastasis enhancement by high expression of aminopeptidase N/CD13. 764 19

Aminopeptidase N (APN, CD13) and dipeptidyl peptidase IV (DPP IV, CD26) are transmembrane ectoenzymes occurring in a wide variety of cells. They are involved in tumour cell invasion and the formation of metastases. A basis for further information about these enzymes is the exact ultrastructural localization in normal and malignant cells. In this paper, we demonstrate the precise subcellular localization of the membrane peptidases APN and DPP IV on the cell surfaces in renal tissues, renal cell carcinoma, cultured renal parenchymal cells and cultured renal carcinoma cells. Using cryo-ultramicrotomy of weakly fixed tissues and cells in combination with indirect immunogold labelling, both membrane peptidases were detectable on the external cell surfaces. They showed different ultrastructural expression patterns. Both membrane peptidases were abundantly labelled on the external cell surfaces of human kidney proximal tubular cells. The expression pattern of APN/CD13 and DPP IV/CD26 in single labelling was confirmed by a successive double labelling technique. The immunolabelling of CD13 on cultured renal parenchymal cells showed a stronger expression then in cells in vivo, but CD26 could not be found. In renal cell cancer (mixed clear cell/chromophilic, poorly differentiated and clear cell type, moderately differentiated) CD13 and CD26 were labelled as in benign renal tissue, but CD26 appeared overexpressed. On the renal carcinoma cells Caki-1 and Caki-2, only one of the two peptidases could be found. CD13 was present non-homogeneously in Caki-1, where the enzyme appeared to form clusters. When CD26 on the cultured renal carcinoma cells Caki-2, is compared with renal proximal tubular cells and renal carcinoma cells in tissue sections, a reduced expression is observed. CD13 was not detected in Caki-2, and CD26 was not found in Caki-1. These small changes on the cell surfaces can only be detected by electronmicroscopic methods. The differences in the distribution of APN/CD13 and DPP IV/CD26 in normal and malignant cells are discussed in connection with literature. Further investigations, especially labelling studies on other neoplastic tissues and cells, will be necessary in order to explain the precise role these membrane peptidases in malignancies.
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PMID:Immunoelectron microscopic demonstration of the membrane proteases aminopeptidase N/CD13 and dipeptidyl peptidase IV/CD26 in normal and neoplastic renal parenchymal tissues and cells. 1096 63

The molecular diversity of the vasculature provides a rational basis for developing targeted diagnostics and therapeutics for cancer. Targeted imaging agents would offer better localization of primary tumors and metastases, and targeted therapies would improve efficacy and reduce side effects. The development of targeted pharmaceuticals requires the identification of specific ligand-receptor pairs, and knowledge of their cellular distribution and accessibility. Using in vivo phage display, a technique by which we can identify organ-specific and disease-specific proteins expressed on the endothelial surface, it is now possible to decipher the molecular signature of blood vessels in normal and diseased tissues. These studies have already led to the identification of peptides that target the normal vasculature of the brain, kidney, pancreas, lung and skin, as well as the abnormal vasculature of tumors, arthritis and atherosclerosis. Membrane dipeptidase in the lungs, interleukin-11 receptor in the prostate, and aminopeptidase N in tumors are examples of molecular targets on blood vessels. Corresponding confocal-microscopic imaging and ultrastructural studies are providing a more complete understanding of the cellular abnormalities of tumor blood vessels, and the distribution and accessibility of potential targets. The combined approach offers a strategy for creating a ligand-receptor map of the human vasculature, and forms a foundation for the development and application of targeted therapies in cancer and other diseases.
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PMID:Probing the structural and molecular diversity of tumor vasculature. 1247 Sep 89

The poor selective toxicity of chemotherapeutic anticancer drugs leads to dose-limiting side effects that compromise clinical outcome. Solid tumors recruit new blood vessels to support tumor growth, and unique epitopes expressed on tumor endothelial cells can function as targets for the anti-angiogenic therapy of cancer. An NGR peptide that targets aminopeptidase N, a marker of angiogenic endothelial cells, was coupled to the surface of liposomal doxorubicin (NGR-SL[DXR]) and was used to treat orthotopic neuroblastoma (NB) xenografts in SCID mice. Pharmacokinetic studies indicated that liposomes coupled to NGR peptide had long-circulating profiles in blood. Their uptake into NB tumor was time dependent, being at least 10 times higher than that of nontargeted liposomes (SL[DXR]) after 24 h, with DXR spreading outside the blood vessels and into the tumors. No uptake was observed into tumors of mice treated with the mismatched peptide ARA-targeted SL[DXR]. Tumor-specific DXR uptake was completely blocked when mice were coinjected with a 50-fold molar excess of the soluble NGR peptide. Adrenal tumor-bearing mice treated with 2 mg/kg/week/x3 of NGR-SL[DXR] partly outlived the control mice (P < 0.001), whereas doses > 3 mg/kg/week/x3 were toxic. Histopathological analysis of cryosections taken from treated mice revealed pronounced destruction of the tumor vasculature with a marked decreased in vessel density. Double staining of tumors with terminal deoxynucleotidyl transferase-mediated nick end labeling and antifactor VIII antibody or antihuman NB demonstrated endothelial cell apoptosis in the vasculature, as well as increased tumor cell apoptosis. Moreover, mice injected with 3 mg/kg/week/x3 of NGR-SL[DXR] displayed rapid tumor regression, as well as inhibition of metastases growth (P = 0.0002). One day after the third treatment, four of six mice showed no evidence of tumors, and the two others showed a >80% reduction in tumor mass and a >90% suppression of blood vessel density (P < 0.01). In contrast, mice treated with ARA-SL[DXR] formed large well-vascularized tumors. Finally, a metronomic administration of NGR-SL[DXR] (1 mg/kg/every other 2 days x 9) induced complete tumor eradication in all animals (P < 0.0001). Our strategy markedly enhanced the therapeutic index of DXR and enabled metronomic administration of therapeutic doses. A dual mechanism of action is proposed: indirect tumor cell kill via the destruction of tumor endothelium by NGR-targeted liposomes and direct tumor cell kill via localization of liposomal DXR to the tumor interstitial space. This combined strategy has the potential to overcome some major limitations of conventional chemotherapy.
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PMID:Vascular damage and anti-angiogenic effects of tumor vessel-targeted liposomal chemotherapy. 1461 39

Aminopeptidase N (APN/CD13), a Zn2+-dependent ectopeptidase, is localized on the cell surface and functions as a transmembrane protein. Increased expression and activity of APN have been postulated to correlate with the aggressive behavior of several tumor types. In this study, the osteosarcoma cell line MNNG/HOS was stably transfected with an expression vector capable of expressing the antisense transcript of APN. Four stably transfected clones, the control clones and parental cells were characterized. Stable integration of the antisense vector was confirmed by PCR analysis of genomic DNA. Competitive RT-PCR revealed that mRNA expression of antisense-transfectants was decreased to approximately 37% of the control cell line. The activity assay showed that the enzymatic activity of APN was inhibited to approximately 51% of the control cell line. Antisense-transfection had no influence on the cellular proliferation measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, on the motility in Transwell chambers, and on the adhesive potential to collagen I. However, an in vitro invasion assay revealed a significant decrease in the number of cells that migrated through a reconstituted membrane (51% of the control cell line). The adhesive potential to Matrigel was also affected (73% of the control cell line). Furthermore, under in vivo conditions, a reduced potency to metastasize to the lung was shown in an experimental metastasis assay in nude mice. These findings demonstrate that APN plays an active role in the cellular attachment and proteolytic degradation of the extracellular matrix in the metastatic process of osteosarcomas.
Clin Exp Metastasis 2003
PMID:Inhibitory effect of antisense aminopeptidase N (APN/CD13) cDNA transfection on the invasive potential of osteosarcoma cells. 1466 89

Due to their extracellular orientation, the ectopeptidases CD10, CD13, CD26, and CD143 have numerous functions, including the post-secretory processing of the neuropeptides and peptide hormones involved in the regulation of growth and differentiation in the gastrointestinal tract. We investigated the transcription and expression pattern of these four ectopeptidases in gastric carcinomas (GC), the corresponding non-neoplastic epithelium, a selection of lymph node metastases (LNM), and the MKN28, AGS, NCI-N87, KATO III gastric cancer cell lines. The gastric foveolar epithelium did not express CD10, CD13, or CD143, but the intestinal metaplasia demonstrated strong immunoreactivity at the brush border for all four ectopeptidases. CD10, CD13, and CD143 were significantly up-regulated in GCs and the lymph node metastases, confirming that they are important for the tumor cell biology. However, there is a lack of correlation between expression in intestinal metaplasia and tumor, as well as in tumor and LNM. Cell proliferation assays were performed with MKN28 and AGS, in which inhibition of CD10 significantly reduced the growth of both cell lines, and inhibition of CD13 significantly increased the proliferation of the AGS cells, indicating that the ability to degrade gastrointestinal peptides may play an important role in the pathobiology of gastric cancer.
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PMID:The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer. 1549 9

Cluster designation (CD) antigens are cell surface markers that can be used to identify constituent cell populations of an organ. We have previously determined the CD phenotype of normal prostate parenchymal cells and are now extending this analysis to prostate cancer. Since expression of CD antigens is associated with cellular differentiation, cancer cells may differ from their normal counterpart in their CD profile. Compared with luminal secretory cells, prostate adenocarcinoma cells are frequently negative for CD10 and CD13, express increased levels of the cell activation molecule CD24, and decreased levels of the apoptosis-associated multifunctional enzyme CD38. Expression of CD57, CD63, CD75s, CD107a, CD107b, CD164, and CD166 by cancer cells is similar to that of secretory cells. Prostate basal epithelial cells do not express the CD antigens characteristic of prostate secretory cells; and the basal cell CD markers, CD29, CD44, CD49b, CD49f, CD104, and nerve growth factor receptor (NGFR) are not expressed by cancer cells. The preferential expression of secretory cell-associated CD markers by prostate cancer cells suggests a closer lineage relationship between cancer cells and secretory cells than basal cells. Although the above cancer CD phenotype was the most frequently seen, some prostate cancers contained populations of CD10- and/or CD13-positive cells, and CD57-negative cells. Furthermore, the cancer phenotype of tumor metastasis is different. Despite its low frequency in primary tumors, CD10 is expressed by virtually all of the nodal metastases of prostate cancer. In addition, stromal fibromuscular cells associated with primary prostate cancer differ from stromal cells in benign prostate tissue by an increased level of expression of the cell activation molecule, CD90. In summary, our data show that the CD marker expression profile of prostate cancer cells most closely resembles that of secretory prostate epithelial cells and that some prostate cancers consist of heterogeneous cell populations as distinguished by CD-marker expression profiles.
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PMID:Heterogeneity in primary and metastatic prostate cancer as defined by cell surface CD profile. 1550 25

Medulloblastoma is a primitive neuroectodermal tumor arising in the posterior fossa usually in the first decade of life. Systemic metastases are infrequent at diagnosis and usually occur after surgical resection or shunt placement. We report a rare case of medulloblastoma in an 18-year-old woman who presented with headache, leukopenia, and anemia. Neurologic examination was normal. Bone marrow evaluation revealed primitive cells morphologically resembling blasts. By flow cytometry, these cells lacked CD45 and expressed CD13/33, CD15, CD34, HLA-DR, and strong CD56. The presence of myeloid antigens and CD34 suggested acute myeloid leukemia; however, the bone marrow core biopsy architecture and tumor cells in cerebrospinal fluid were more compatible with a nonhematopoietic tumor. Further workup revealed a cerebellar mass, and a diagnosis of desmoplastic medulloblastoma was made. To our knowledge, this is the first reported case of a nonhematopoietic small round blue-cell tumor expressing multiple myeloid antigens and CD34 by flow cytometry.
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PMID:Medulloblastoma simulating acute myeloid leukemia: case report with a review of "myeloid antigen" expression in nonhematopoietic tissues and tumors. 1748 18

We report clinicopathologic features of a large series of renal translocation carcinomas from a multicentric study. Diagnosis was performed by cytogenetic examination of fresh material and/or by immunochemistry with antibodies directed against the C-terminal part of transcription factor E3 (TFE3) and native transcription factor EB (TFEB) proteins. Clinical data, follow-up, and histologic features were assessed. Antibodies against CK7, CD10, vimentin, epithelial membrane antigen, AE1-AE3, E-cadherin, alpha-methylacyl-coenzyme A racemase, melan A, and HMB45 were tested on tissue microarrays. Whole-genome microarray expression profiling was performed on 4 tumors. Twenty-nine cases were diagnosed as TFE3 and 2 as TFEB renal translocation carcinomas, including 13 males and 18 females, mean age 24.6 years. Two patients had a previous history of chemotherapy and 1 had a history of renal failure. Mean size of the tumor was 6.9 cm. Thirteen cases were > or = pT3 stage. Twelve cases were N+ or M+. Mean follow-up was 29.5 months. Three patients presented metastases and 5 have died. Mixed papillary and nested patterns with clear and/or eosinophilic cells represented the most consistent histologic appearance, with common foci of calcifications regardless of the type of translocation. Using a 30 mn incubation at room temperature, TFE3 immunostainings were positive in only 82% of our TFE3 translocation carcinomas. Both TFE3 and TFEB renal translocation carcinomas expressed CD10 and alpha-methylacyl-coenzyme A racemase in all cases. An expression of E-cadherin was observed in two-third of cases. Cytokeratins were expressed in less than one-third of cases. Melanocytic markers were expressed at least weakly in all cases except two. Unsupervised clustering on the basis of the gene expression profiling indicated a distinct subgroup of tumors. TRIM 63 glutathione S-transferase A1 and alanyl aminopeptidase are the main differentially expressed genes for this group of tumors. Our results suggest that these differentially expressed genes may serve as novel diagnostic or prognostic markers.
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PMID:Renal translocation carcinomas: clinicopathologic, immunohistochemical, and gene expression profiling analysis of 31 cases with a review of the literature. 1834 67


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