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)

It is the relentless invasion and growth into surrounding tissue that characterize oral squamous cell carcinoma. Metastasis is perhaps the most challenging and important aspect of cancer progression, in that it generally signifies limited survival and ineffective therapy. Inherent in metastasis is invasion, the process by which cells infiltrate into adjacent tissues, degrading basement membranes and extracellular matrix and disrupting tissue architecture and sometimes organ function. The factors that regulate these processes are complex and likely involve loss of the controls that are normally in place in physiologic tissue modeling. Adhesion receptors and their ligands are important in modulating not only invasion of oral squamous cell carcinoma cells but also their survival and proliferation. Normal oral mucosal epithelial cells use integrins to maintain their anchorage to the basement membrane, whereas the formation of stratifying cell layers depends on the formation of intercellular adhesions mediated by cadherins. The process of squamous cell carcinoma invasion and dissemination requires active cell migration through the extracellular matrix with the simultaneous remodeling of intercellular adhesions. Integrins are clearly important in the invasive process, whereas intercellular adhesion receptors restrain invasion and promote a more differentiated phenotype.
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PMID:Adhesive mechanisms regulating invasion and metastasis in oral cancer. 1180 19

Adhesion molecules are transmembrane proteins that can anchor cytoskeletal proteins on the cytoplasmic side of the cell membrane, while also connecting extracellular structures on the outer surface of the cell membrane. In addition to physical linkages between the extracellular environment and the cytoskeleton, adhesive complexes participate in important signal transduction systems as modulators or receptors. Their functions in cell signaling are probably at least as important as their cytoskeletal and cell attachment properties. Understanding these regulatory functions appears to be of importance in determining of pathological characteristic of numerous diseases. Expression and functional activity of various adhesion molecules have been found in different diseases affecting the colorectum. In this review we summarize recent advantages about the cell biology these diseases and clinical implications.
Clin Exp Metastasis 2000
PMID:Cell biology and clinical implications of adhesion molecules in colorectal diseases: colorectal cancers, infections and inflammatory bowel diseases. 1182 66

The tumor microenvironment is often overlooked when considering tumor response to chemotherapeutic agents. This environment consists of soluble factors, components of the extracellular matrix as well as cell-cell interactions. Recently, it has become clear that cell-cell and cell-matrix interactions result in cytoskeletal reorganization and the activation of multiple signal transduction pathways that directly influence cell survival, growth and differentiation. Experimental evidence shows that anti-apoptotic pathways initiated by cell adhesion are operative in tumor cells and, furthermore, cause resistance to mechanistically distinct cytotoxics. For hematopoietic tumors, cell adhesion to a single matrix, fibronectin is sufficient to inhibit apoptosis induced by mechanistically distinct cyctotoxics. Adhesion of hematopoietic tumors to this matrix blocks cell cycle progression, and for the human multiple myeloma 8226 cell line adhesion to fibronectin resulted in increased p27kip1 levels, which correlated with cell cycle arrest and drug resistance. A decrease in initial DNA damage induced by topoisomerase II inhibitors has also been observed in adherent hematopoietic tumor cell lines. Further studies investigating the mechanisms of cell adhesion mediated drug resistance may reveal novel targets directed at the reversal of de novo drug resistance.
Cancer Metastasis Rev 2001
PMID:Mechanisms associated with cell adhesion mediated drug resistance (CAM-DR) in hematopoietic malignancies. 1183 46

Breast and prostate cancer preferentially metastasize in the skeleton, inducing locally increased bone resorption by osteoclasts. Bisphosphonates (BPs), potent inhibitors of osteoclasts and bone resorption, are able to reduce metastatic bone lesions, but the metastasis-related cellular target molecules for BPs have not yet been identified. In osteoclasts, nitrogen-containing BPs inhibit the function of the mevalonate pathway, impairing the prenylation and activation of small GTPases. In addition, direct effects of BPs on cancer cells have been suggested. In the present study, the effects of two clinically used BPs, the amino-BP alendronate and clodronate, on adhesion, invasion, and migration of human PC-3 prostate cancer cells were examined in vitro. We also studied the possible role of the mevalonate pathway in invasion and migration of PC-3 cells using the beta-hydroxy-beta-methylglutaryl-CoA reductase inhibitor mevastatin and the mevalonate pathway intermediates mevalonate (mevalonic acid lactone), geranylgeraniol, and trans-trans-farnesol. The results demonstrate that alendronate pretreatment very effectively inhibited in vitro invasion of prostate cancer cells in a dose-dependent manner, with an IC50 as low as approximately 1 pM. The inhibition was similar to that of mevastatin. Clodronate also inhibited invasion, but the IC50 was 0.1 microM. Importantly, geranylgeraniol and trans-trans-farnesol reversed the inhibitory effect of alendronate and mevastatin but not the clodronate-induced inhibition of invasion. Alendronate pretreatment also inhibited migration, which was partially reversed by geranylgeraniol and trans-trans-farnesol. Adhesion of PC-3 cells to various matrices was reduced, and their F-actin organization was changed. Alendronate pretreatment also inhibited invasion of human Du-145 prostate and MDA-MB-231 breast cancer cells. As a conclusion, the results demonstrate that the mevalonate pathway leading to protein prenylation is important for cancer cell invasion and migration in vitro. They further suggest that interference with this pathway is involved in inhibition of invasion and migration of prostate cancer cells by the amino-BP alendronate but that the mechanism of clodronate inhibition is different. It is possible that BPs have therapeutic potential in preventing the spread of prostate cancer.
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PMID:Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway. 1508 15

The invasion of malignant cells through the basement membrane is a critical step in local infiltration and metastasis. Adhesion and invasion of malignant cells may be modulated by their receptor mediated binding to the basement membrane glycoprotein-laminin. Laminin consists of the sequences with anticancer and antimetastatic activity. Its peptide fragment YIGSR is known to inhibit the experimental metastases of several tumors. This sequence and a tripeptide RGD of laminin inhibits both angiogenesis and tumor growth. In contrary, the sequence SIKVAV initiates angiogenesis and tumor progression. Moreover, laminin plays also other functions in human organism. One of them is the influence on platelet aggregation and thrombogenesis.
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PMID:[Biological activity of synthetic analogs of laminin active sequences: YIGSR, RGD, SIKVAV]. 1258 26

Colon cancer preferentially metastasizes to the liver. To determine cellular backgrounds of this preference, we generated an enhanced green fluorescent protein (eGFP)-expressing rat adenocarcinoma cell line (CC531s) that forms metastases in rat liver after administration to the portal vein. Intravital videomicroscopy (IVVM) was used to visualize early events in the development of tumors in livers of live animals from the time of injection of the cancer cells up to 4 days afterward. Based on information obtained with IVVM, tissue areas were selected for further analysis using confocal laser scanning microscopy (CLSM), electron microscopy (EM), and electron tomography. It was shown that initial arrest of colon cancer cells in sinusoids of the liver was due to size restriction. Adhesion of cancer cells to endothelial cells was never found. Instead, endothelial cells retracted rapidly and interactions were observed only between cancer cells and hepatocytes. Tumors developed exclusively intravascularly during the first 4 days. In conclusion, initial steps in the classic metastatic cascade such as adhesion to endothelium and extravasation are not essential for colon cancer metastasis in liver.
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PMID:Visualization of early events in tumor formation of eGFP-transfected rat colon cancer cells in liver. 1457 75

Despite some success in the treatment of colorectal carcinomas, novel rational therapies targeting specific cancer-related molecules are under development and urgently needed. These approaches need careful preclinical evaluation in models that closely mirror the clinical situation. Therefore, we established a panel of 15 xenotransplantable tumours directly from fresh surgical material. We showed that both the histology and expression of tumour-associated markers (Epithelial Cell Adhesion molecule (EpCAM), E-cadherin, carcinoembryonic antigen (CEA)) could be maintained during passaging in nude mice. Xenotransplanted tumours were characterised for chemosensitivity and revealed a response rate of 5/15 (33%) for 5-fluorouracil (5-FU), 15/15 (100%) for irinotecan and 8/14 (57%) for oxaliplatin. 5 patients out of 15 were treated with cytostatics because of synchronous metastases. The response to chemotherapy in these patients coincided very closely with the response of the individual xenografts. All of the xenografts expressed the proliferation marker Ki67 and the nuclear enzyme, Topoisomerase IIalpha (Topo IIalpha) at the protein level. Most of the xenografts also expressed the tumour suppressor, p53 (9/14) and the nuclear enzyme Topoisomerase Ialpha (Topo Ialpha) (13/14) at the protein level. Interestingly, the presence of a K-ras mutation in codon 12 (5/15 xenografts) coincided with a low response rate towards oxaliplatin. This observation needs further confirmation using a larger number of tumours. In conclusion, we were able to establish transplantable xenografts suitable to mimic the clinical situation. These well characterised models are useful tools for the preclinical development of novel therapeutic approaches and for investigating translational research aspects.
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PMID:Anticancer drug response and expression of molecular markers in early-passage xenotransplanted colon carcinomas. 1472 46

Anoikis is apoptosis induced by loss of cell adhesion or inappropriate cell adhesion. Adhesion on the extracellular matrix is important to determine whether a cell is in the correct location and to delete displaced cells by apoptosis. The ability to overcome this requirement has important implications for metastatic cancer. However, how adhesion signals are interpreted by a cell into a life or death decision is complex. In this paper, we will examine this from the point of view of the apoptotic machinery of the cell, and discuss the various ways in which adhesion can influence this process.
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PMID:Anoikis. 1515 51

Adhesion of tumor cells to endothelium via cell-adhesion molecules constitutes a crucial step in metastasis, which is largely responsible for the poor prognosis of small-cell lung carcinoma (SCLC). Patients with SCLC were reported to have elevated levels of intercellular adhesion molecule-1 (ICAM-1). The present study therefore focusses on endothelial ICAM-1 in tumor-cell adhesion. We found that the adherence of SCLC cells (cell lines H24, H69, H82) to cultured vascular endothelium in stasis and flow depends on the expression of ICAM-1. After blocking endothelial ICAM-1 with monoclonal antibodies, adhesion was significantly reduced. These results pinpoint ICAM-1 for the first time as a molecule crucially involved in SCLC cell-endothelial adhesion.
Clin Exp Metastasis 2004
PMID:ICAM-1 supports adhesion of human small-cell lung carcinoma to endothelial cells. 1538 68

Mesothelial cell intercellular adhesion molecule-1 (ICAM-1) has recently been shown to play a role in tumour cell adherence to the peritoneum. However, solid tumours poorly express its most ubiquitous ligand, beta2 integrin. The aim of this study was to investigate the role of the beta2 integrin subunit and CD43, a known ligand for ICAM-1, in the development of peritoneal metastases. beta2 Integrin subunit and CD43 expression was assessed on a number of tumour cell lines. Adhesion of SW1222 and PSN-1 cells to human peritoneal mesothelial cells was investigated using a fluorometric assay incorporating an inhibitory antibody to beta2 integrin and CD43. beta2 Integrin expression was not inducible on these tumour cell lines, but Western blotting demonstrated CD43 expression in all the cancer cell lines examined and cell surface expression was confirmed by flow cytometry. The anti-CD43 antibody significantly reduced adhesion of PSN-1 and SW1222 cells to HPMC, however beta2 integrin inhibition did not reduce tumour cell adhesion. CD43 is expressed by a variety of carcinoma cell lines, and plays a role in tumour cell-peritoneal adhesion probably via interactions with its putative ligand ICAM-1.
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PMID:Tumour-expressed CD43 (sialophorin) mediates tumourmesothelial cell adhesion. 1544 12


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