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)

One important application of DNA microarray technology is the simultaneous analysis of gene expression of different mRNAs. Comparison of mRNA patterns of diseased and healthy tissue may help to understand the pathogenesis of a given disorder. In cancer tissue, identified dysregulated genes may serve as new molecular markers for diagnosis or prognosis or may ideally serve as new targets for therapy. Using membrane cDNA array technology, we analyzed gene expression in human melanomas, one of the most aggressive types of cancer with a high metastatic potential and with markedly increased incidence worldwide. To account for the heterogeneity of tumors, we compared total RNA from cutaneous melanoma metastases of 10 different patients with primary human melanocytes. An abundance of genes was dysregulated (up-/downregulated), which involved for example the apoptosis gene growth factor receptor-bound protein 10, Bcl2-associated X membrane protein, Bcl2 antagonist of cell death, glutathione S-transferase theta(1) and glutathione reductase. Ultimately, the identification of melanoma-associated genes may provide a potential therapeutic strategy for identifying and targeting malignant melanoma.
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PMID:Rapid identification of dysregulated genes in cutaneous malignant melanoma metastases using cDNA technology. 1538 85

The aim of the study was to investigate the relationship between the expression of the HER-2 membrane protein and other clinical-pathological parameters such as: histological size of the tumor, degree of the tumor's differentiation, presence of vascular invasion and presence of metastases in regional lymph nodes, in cases of ductal infiltrative breast cancer. We have investigated 56 cases of ductal infiltrative breast cancer. In all patients a mastectomy with a dissection of axillary lymph nodes has been performed. All tissue samples, taken by biopsy, were embedded in the paraffin, stained by hematoxylin-eosin technique and screened, and evaluation was performed by using a semiquantitative method of the immunohistochemical expression of the HER-2 protein. A decrease of the protein HER-2 expression was noticed in cases of an increase of the tumor's diameter above 50 mm. Increased expression of the HER-2 protein was noticed in cases of moderate (grade II) and poor (grade III) differentiation of carcinoma, as well as in cases where there was no metastases in the regional lymph nodes. No relationship has been observed between the expression of HER-2 and occurrence of vascular invasion. In cases of ductal infiltrative breast cancer the expression of HER-2 protein is in correlation with the size and degree of tumor's differentiation, as well as with the presence of metastases in regional lymph nodes.
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PMID:Correlation of the HER-2 protein expression and other clinicopathological features of ductal infiltrative breast cancer. 1577 95

Adhesive interactions between the molecules on cancer cells and the target organ are one of the key determinants of the organ specific metastasis. In this communication we show that b1,6 branched N-oligosaccharides which are expressed in a metastasis-dependent manner on B16-melanoma metastatic cell lines, participate in the adhesion process. We demonstrate that high metastatic cells show significantly increased translocation of one of the major carriers of these oligosaccharides, lysosome associated membrane protein (LAMP1), to the cell surface. LAMP1 on high metastatic cells, carry very high levels of these oligosaccharides, which are further substituted with poly N-acetyl lactosamine (polylacNAc), resulting in the expression of high density of very high affinity ligands for galectin-3 on the cell surface. We show that galectin-3 is expressed in highest amount in the lungs as compared to other representative organs. Blocking galectin-3 by pre-incubating the frozen sections of the lungs with 100 mM lactose, substantially inhibited the adhesion of high metastatic cells, while pre-incubation with sucrose had no effect. Finally, by in situ labeling and immunoprecipitation experiment, we demonstrated that the lung vascular endothelial cells express galectin-3 constitutively on their surface. Galectin-3 on the organ endothelium could thus serve as the first anchor for the circulating cancer cells, expressing high density of very high affinity ligands on their surface, and facilitate organ specific metastasis.
Clin Exp Metastasis 2005
PMID:Altered melanoma cell surface glycosylation mediates organ specific adhesion and metastasis via lectin receptors on the lung vascular endothelium. 1613 74

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 microM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 +/- 3.9% in HNE1-LMP1 cells vs 37.89 +/- 4.9% in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 +/- 3.5 vs 65.87 +/- 5.9%), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 +/- 3.7 and 27.91 +/- 2.1%), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 +/- 3.9 vs 29.19 +/- 6.27%) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.
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PMID:Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro. 1664 6

Lysosome-associated membrane protein-1 is a protein with a significant content of beta1,6-branched N-glycans. It is thought that enhanced expression of lysosome-associated membrane protein-1 in tumour cells may promote invasion by influencing both adhesion to extracellular matrix and perhaps also binding to endothelial cells. The present study was aimed at examining levels of lysosome-associated membrane protein-1 in human melanomas and benign pigmented lesions to evaluate whether this protein might be considered a potential molecular marker of melanoma progression. The expression of lysosome-associated membrane protein-1 was for the first time determined immunohistochemically in formalin-fixed paraffin-embedded specimens comprising 42 primary cutaneous melanomas, 15 lymph node melanoma metastases (11 correlated with primary tumours), three melanoma recurrences (correlated with both primary and metastatic melanomas), 27 nevi and four epithelial tumours (two seborrhoeic keratoses and two basal cell carcinomas). Our results demonstrate that development and progression of melanoma are associated with changes of the lysosome-associated membrane protein-1 level. The expression was strongest in melanoma recurrences and lymph node metastases, weaker in primary cutaneous melanomas and not detectable in melanocytes of pigmented nevi. Nodular melanomas expressed lysosome-associated membrane protein-1 at higher level than superficially spreading melanomas.
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PMID:Different expression of lysosome-associated membrane protein-1 in human melanomas and benign melanocytic lesions. 1671 70

Vacuole membrane protein 1 (Vmp1) is described as a cancer-relevant cell cycle modulator, but the function of this protein and its mode of action in tumor progression are still unknown. In this study, we show that the VMP1 mRNA level is significantly reduced in kidney cancer metastases as compared to primary tumors. Further, VMP1 expression is also decreased in the invasive breast cancer cell lines HCC1954 and MDA-MB-231 as compared to the non-invasive cell lines MCF-12A, T-47D and MCF-7. We show for the first time that Vmp1 is a plasma membrane protein and an essential component of initial cell-cell contacts and tight junction formation. It interacts with the tight junction protein Zonula Occludens-1 and colocalizes in spots between neighboring HEK293 cells. Downregulation of VMP1 by RNAi results in loss of cell adherence, and increases the invasion capacity of the non-invasive kidney cancer cell line Caki-2. In conclusion, our findings establish Vmp1 to be a novel cell-cell adhesion protein and that its expression level determines the invasion and metastatic potential of cancer cells.
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PMID:Reduced expression of vacuole membrane protein 1 affects the invasion capacity of tumor cells. 1772 69

C4.4A is a glycolipid-anchored membrane protein with structural homology to the urokinase-type plasminogen activator receptor (uPAR). Although C4.4A was identified as a metastasis-associated protein little is known about its actual expression and possible function in malignant disease. In the present study, we have therefore analyzed the expression of C4.4A in 14 esophageal squamous cell carcinomas (ESCC). Normal squamous esophageal epithelium shows a strong cell surface associated C4.4A expression in the suprabasal layers, whereas basal cells are negative. Upon transition to dysplasia and carcinoma in situ the expression of C4.4A is abruptly and coordinately weakened. Double immunofluorescence staining of normal and dysplastic tissue showed that C4.4A colocalizes with the epithelial cell surface marker E-cadherin in the suprabasal cells and has a complementary expression pattern compared to the proliferation marker Ki-67. A prominent, but frequently intracellular, C4.4A expression reappeared in tumor cells located at the invasive front and local lymph node metastases. Because C4.4A was reported previously to be a putative laminin-5 (LN5) ligand, and both proteins are expressed by invasive tumor cells, we analyzed the possible coexpression of C4.4A and the gamma 2-chain of LN5 (LN5-gamma 2). Although these proteins are indeed expressed by either neighboring cancer cells or in a few cases even coexpressed by the same cells in the tumor front and metastases, we found no evidence for a general colocalization in the extracellular compartment by confocal microscopy. In conclusion, C4.4A is expressed during invasion and metastasis of human ESCC and may thus provide a new histological marker in this disease.
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PMID:Altered expression of the urokinase receptor homologue, C4.4A, in invasive areas of human esophageal squamous cell carcinoma. 1784 75

Morphogenesis of malignant tumors is characterized by proliferation, invasive growth and metastasis. Although these properties are determined mainly by genetic derangements, their biological behavior within tissues is strictly regulated by tumor microenvironment, which consists of extracellular matrix, proteinases, soluble factors (cytokines/growth factors/chemokines), stromal cells and blood vessels. Thus, modulation of the microenvironment is implicated in morphogenesis in tumorigenesis. ADAMs (a disintegrin and metalloproteinases) are a new gene family of membrane-anchored and secreted proteins that have proteolytic and/or adhesive properties. They are involved in biological events including cell adhesion, cell fusion, membrane protein shedding and proteolysis. We examined the expression of the proteinase-type ADAMs in the invasive breast and lung carcinoma tissues, and found that membrane-anchored ADAM28m and secreted ADAM28s are selectively overexpressed in activated forms by carcinoma cells. The mRNA expression levels directly correlated with the proliferative activity of the carcinoma cells in both carcinomas, and with lymph node metastasis in the lung carcinomas. Our experimental studies showed that ADAM28 plays a key role in cancer cell proliferation through enhancing bioavailability of insulin-like growth factor-I (IGF-I) released from the IGF-I/IGF-binding protein 3 (IGFBP-3) complex by selective cleavage of IGFBP-3. We also identified P-selectin glycoprotein ligand-1 (PSGL-1) as a binding protein to ADAM28 by yeast two-hybrid system, and demonstrated that ADAM28s promotes PSGL-1/P-selectin-mediated HL-60 cell rolling adhesion to endothelial cells and subsequent transendothelial migration into tissue spaces. Altogether, our data suggest the possibility that ADAM28 expressed by cancer cells is involved in cancer cell proliferation and metastases in human cancers through modulation of tumor microenvironment and cell adhesion.
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PMID:Modulation of the microenvironment and adhesion of cancer cells by ADAMs (a disintegrin and metalloproteinase). 1831 93

The identity and functions of surface proteins on human leptomeningeal and meningioma cells are incompletely characterized. Some structural and functional similarities between the leptomeninges and pleura suggest that proteins important to pleural function and tumorigenesis might also be relevant to leptomeningeal disease. Mesothelin is a recently described, 40-kDa membrane protein expressed in pleura. Its functions in this tissue are under investigation. Sections of 20 normal adult brains with leptomeninges and 49 World Health Organization (WHO) grade I, 21 grade II, and 2 grade III meningiomas were analyzed using an extensively characterized monoclonal antibody to mesothelin and streptavidin-biotin complex immunohistochemistry. Five meningiomas were also evaluated by Western blot. Mesothelin immunoreactivity was detected in the arachnoid in 6 of 20 cases and in 23 of 49 WHO grade I meningiomas. It was also detected in 7 of 21 WHO II tumors and 1 of the 2 anaplastic meningiomas. By Western blot, all five meningiomas exhibited mesothelin precursor protein, including one where notable immunoreactivity was not identified in a formalin-fixed tissue section. These findings suggest that mesothelin is expressed in at least some arachnoid and meningioma cells. Future studies may clarify its role in the development of meningiomas, meningeal seeding of gliomas, and metastases to the leptomeninges.
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PMID:Mesothelin expression in the leptomeninges and meningiomas. 1834 77

Prostate cancer is the most common non-cutaneous cancer of men in the United States and represents their second-leading cause of cancer-related death. Metastatic disease is largely resistant to conventional chemotherapies, and targeted therapies are urgently needed. Prostate-specific membrane antigen (PSMA) is a prototypical cell-surface marker of prostate cancer. PSMA is an integral, non-shed, type 2 membrane protein with abundant and nearly universal expression in prostate carcinoma, but has limited extra-prostatic expression. In addition, PSMA is expressed in the neovasculature of other solid tumors. These findings have spurred development of PSMA-targeted therapies for cancer, and first-generation products have entered clinical testing. Vaccine approaches have included recombinant protein, nucleic acid and cell-based strategies, and anti-PSMA immune responses have been demonstrated in the absence of significant toxicity. Therapy with drug-conjugated and radiolabeled antibodies has yielded objective clinical responses as measured by reductions in serum prostate-specific antigen and/or imageable tumor volume. However, responses were observed in a minor fraction of patients and at doses near the maximum tolerated dose. Overall, these initial studies have provided measured proof of concept for PSMA-based therapies, and second-generation antibody and vaccine products may hold the key to exploit PSMA for molecularly targeted therapy of prostate and other cancers.
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PMID:Clinical trials of cancer therapies targeting prostate-specific membrane antigen. 1847 4


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