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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cells of various normal and malignantly transformed tissues are connected by "adhering junctions"-plasma membrane domains characterized by close membrane-membrane contact, a dense cytoplasmic plaque and, in most cases, the attachment of cytoskeletal filaments. On the basis of their specific ultrastructural organization and molecular composition, three major types of intercellular adhering junctions can be distinguished: 1. Adherens junctions appear in different shapes and sizes (zonula adhaerens, fascia adh., punctum adh.) and contain the transmembrane glycoprotein E-cadherin. The cytoplasmic portion of E-cadherin forms complexes with alpha-, beta-, and gamma-catenin and plakoglobin which, together with other proteins such as vinculin and radicin, constitute a plaque at which actin microfilaments insert. 2. Desmosomes (maculae adhaerentes) are mostly isodiametric (diameters up to approximately 0.5 micron) membrane domains traversed by representatives of two types of desmosomal cadherins, the desmogleins (Dsg) and desmocollins (Dsc), whose cytoplasmic tails contribute to a dense plaque containing plakoglobin and desmoplakin I (with or without an alternative splice form, desmoplakin II) which anchor IFs. The specific Dsc and Dsg subtypes can differ in different cell types and up to three different human genes have so far been identified for each desmosomal cadherin. 3. Complexus adhaerentes are junctions of variable size and shape that occur in lymphatic endothelia. They have a desmoplakin- and plakoglobin-rich plaque, whose specific transmembrane proteins have not yet been fully elucidated but can include endothelial cadherin-5. In their most elaborate subform- the "syndesmos" connecting the retothelial cells of lymph node sinus-these junctions can occupy extended portions of the cell surface. The molecular arrangements in desmosomes and complexus adhaerentes have been studied to understand the assembly and disappearance of these structures. The diagnostic potential of their constituent proteins for cell typing in tumor diagnosis is emphasized, as is the role of transient junction dissociation during invasion and metastasis of carcinomas and the general importance of tumor cell interactions with the retothelial cell system in the formation of lymph node metastases.
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PMID:The desmosome and the syndesmos: cell junctions in normal development and in malignancy. 898 60

E-selectin which is expressed on endothelial cells plays an important role in the adhesion of cancer cells to the vascular endothelium, being the ligand for a carbohydrate antigen expressed on cancer cells. In this study, the clinical usefulness of this protein was examined. E-selectin was expressed on the endothelial cells of the small vessels adjacent to the cancer nests in 63 of the 104 (60.6%) primary tumors of breast cancer. The expression of E-selectin in locations adjacent to the cancer nests was more pronounced than that in distant ones. The mean value of serum soluble E-selectin (ng/ml) was 38.3 in benign breast disease, 47.8 in those with no evidence of recurrence, 49.4 in stage I/II primary breast cancer, 75.8 in stage III/IV primary breast cancer, and 93.7 in recurrent breast cancer. The mean value of serum soluble E-selectin was 106.2 ng/ml in patients with distant metastases, and 50.4 ng/ml in those with no evidence of distant metastases. Thus, the concentration of soluble E-selectin was significantly elevated in the sera of patients with distant metastases. These findings suggested that cancer cells induced the expression of E-selectin on endothelial cells and, that serum soluble E-selectin is useful as a tumor marker having a close relationship to metastasis in breast cancer.
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PMID:Increased concentration of soluble E-selectin in the sera of breast cancer patients. 913

The adhesion of circulating cancer cells to the vascular endothelium is an important at step in the hematogenous metastasis of cancer. E-selectin expressed on endothelial cells and carbohydrate ligands expressed on cancer cells mediate this adhesion. We investigated the clinical significance of such cell adhesion molecules in breast cancer. The cytosol concentration of sialyl Lewis(x) was found more elevated in cancerous tissue than that in adjacent non-cancerous tissue. In the serum, sialyl Lewis(x) and soluble E-selectin were seen elevated in patients with advanced and recurrent breast cancer, especially in those with distant metastases. From the above, we have concluded that sialyl Lewis(x) and soluble E-selectin could be used as tumor markers with a close relationship to the metastasis of breast cancer.
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PMID:Increased level of circulating adhesion molecules in the sera of breast cancer patients with distant metastases. 925 66

The ability of a tumor cell to survive is critical for successful dissemination to sites distant from the primary tumor. Tumor cells must enter blood circulation, resist hemodynamic shear stress of the blood circulation, successfully extravasate, and then migrate through dense tissue stroma to a site favorable for tumor growth. Some tumor cells must therefore be endowed with peculiar abilities to successfully metastasize, whereas others, although capable of forming tumor in specific organs, cannot metastasize. This property has often been associated with the homing ability of a given tumor cell, likely through the expression of organ-specific homing receptors that are critical for the extravasation process. The present work was aimed at establishing the point at which metastatic and nonmetastatic lymphoma cells diverge. Although 164T2 and 267T2 lymphoma cell lines can successfully form thymic lymphoma when injected intrathymically, only the 164T2 clone can efficiently form tumor in kidneys, spleen, and liver after intravenous inoculation. Using the indium-labeling technique to monitor the homing kinetic of both cell lines, we showed that the critical step for the successful metastasis of the lymphoma cell was determined in the final steps of the disseminating process, namely after homing. These results indicate that, whereas binding of tumor cells to vascular endothelium through specific adhesion mechanisms is a prerequisite for dissemination of tumor cells, the resistance of a tumor cell to the antagonist action of the host and/or its ability to grow tumor occurs only after homing to the target organ.
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PMID:The metastatic characteristics of murine lymphoma cell lines in vivo are manifested after target organ invasion. 942 18

Tumor cell extravasation is a determinant step in the process of hematogenous metastasis. The signal transduction pathways involved in the interactions between tumor cells and the vascular endothelium during transendothelial migration are still undefined. In the present study, we have investigated the influence of human breast adenocarcinoma cells (MCF7) on human umbilical vein endothelial cell (HUVEC) intracellular Ca2+ concentration ([Ca2+]i). We show that the contact between MCF7 cells and a confluent HUVEC monolayer induces an immediate and transient increase in HUVEC [Ca2+]i. This [Ca2+]i rise could not be elicited by tumor cell-conditioned medium, isolated tumor cell membranes, inert beads or normal breast epithelial cells, demonstrating the involvement of specific recognition mechanisms between MCF7 cells and HUVEC. Depletion of HUVEC intracellular Ca2+ stores by the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin as well as the selective depletion of inositol 1,4,5-triphosphate (IP3)-sensitive Ca2+ stores by prior activation of HUVEC using histamine resulted in a complete inhibition of tumor cell-induced [Ca2+]i elevation. Similar results were obtained when HUVEC monolayers were treated with the tyrosine kinase inhibitor herbimycin A, suggesting a role for tyrosine kinase-associated cell surface receptors in tumor cell-endothelial cell interactions. The depletion of HUVEC intracellular Ca2+ stores by thapsigargin was also shown to delay MCF7-induced endothelial cell disjunction, to prevent their spreading on the subendothelial extracellular matrix and transendothelial migration in vitro. These results suggest that transient changes in endothelial [Ca2+]i may govern multiple steps of tumor cell extravasation.
Clin Exp Metastasis 1998 Jan
PMID:Endothelial cell intracellular Ca2+ concentration is increased upon breast tumor cell contact and mediates tumor cell transendothelial migration. 950 74

Nitric oxide (NO) is a free radical molecule with high reactivity, a short half life and a variety of physiological activities. The role of NO in tumor microcirculation, based on the data collected to date, can be summarized as follows: 1) NO may partially mediate tumor angiogenesis; 2) endogenous NO derived from tumor vascular endothelium and/or tumor cells increases and/or maintains tumor blood flow via dilatation of arteriolar vessels, decreases leukocyte-endothelial interaction, and increases vascular permeability; 3) exogenous NO can increase tumor blood flow via vessel dilatation, and reduce vessel tone; and 4) NO production rates and vascular response to NO are heterogeneous and tumor-dependent. Modulation of NO level in tumor vessels can alter tumor hemodynamics and thus augment oxygen, drug, gene vector and effector cell delivery to solid tumors.
Cancer Metastasis Rev 1998 Mar
PMID:Role of nitric oxide in angiogenesis and microcirculation in tumors. 954 24

Canine osteosarcoma is a prevalent bone neoplasm which has similarities to the human disease. We used a retrospective study to investigate the possibility that tumor vascularity may provide useful prognostic information, indicative of the role of this parameter in progression of this cancer. We quantified microvessel density in 52 histological specimens of primary tumor, immunostained for von Willebrand's Factor to identify vascular endothelium. For the 20 cases not euthanized at presentation or lost to follow-up, we found significantly higher tumor microvascular densities in animals presenting with detectable pulmonary metastases (5 of 20), and significantly lower densities in animals without metastatic disease at presentation, but later surviving to develop pulmonary metastases (7 of 20; P < 0.05). Animals with no evidence of pulmonary metastases at time of death (8 of 20) had intermediate vascular densities in their tumors. The results of this preliminary study suggest that vascularity of the primary tumor may be an indication of tumor progression. Future studies with a larger number of cases should establish whether vascular density can be a useful prognostic parameter for canine osteosarcoma.
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PMID:Blood vessel density in canine osteosarcoma. 968 49

Oral glucosamine has anti-inflammatory activity in rodents, and anecdotal evidence suggests that it may be clinically useful in inflammatory bowel disorders. A possible explanation is that supplemental glucosamine increases production of heparan sulfate (HS) proteoglycans by the vascular endothelium, thereby improving the endothelium's barrier function. Extravasation of leukocytes and metastatic cancer cells requires degradation of HS. Heparin can inhibit neutrophil activation, adhesion, and chemotaxis, and--like glucosamine--has been reported effective for managing inflammatory bowel syndromes. Cytokine-mediated loss of endothelial HS may be a key factor in the coordinated inflammatory response. These considerations suggest that glucosamine may have clinical utility in a range of inflammatory disorders, and should be assessed with regard to its impact on cancer metastasis and peripheral ischemic disease. In inflammatory bowel disease, fish oil, ginkgolides, and enteric-coated 5-aminosalicylic acid may safely complement the efficacy of glucosamine.
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PMID:Vascular heparan sulfates may limit the ability of leukocytes to penetrate the endothelial barrier--implications for use of glucosamine in inflammatory disorders. 988 30

Integrins are receptors that mediate cell adhesion and the formation of signaling complex. Changes in the expression of integrins are required during the following steps in the generation of metastases: a) angiogenesis; b) detachment from the primary tumor; c) tumor cell-platelet interaction; d) adhesion to vascular endothelium and e) proliferation. There is a correlation between invasive capability and changes in the expression of some proteins that are clustered in focal adhesion sites, as FAK, CD82, CD9 or CD63. Both, integrin blocking (using antibodies or RGD containing peptides), as well as induced changes in the expression of integrin-associated molecules, are able to inhibit formation of metastases. Discovery and characterization of molecules that regulate the adhesive capability of tumor cells, will lead to development of antimetastasic therapies. In the search of tumor dissemination inhibitors, integrins and some integrin-associated molecules are important pharmacological targets.
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PMID:[Integrins and integrin-associated molecules: targets for the development of antimetastatic therapies]. 1046 9

Metastasis is a frequent complication of cancer, yet the process through which circulating tumor cells form distant colonies is poorly understood. We have been able to observe the steps in early hematogenous metastasis by epifluorescence microscopy of tumor cells expressing green fluorescent protein in subpleural microvessels in intact, perfused mouse and rat lungs. Metastatic tumor cells attached to the endothelia of pulmonary pre-capillary arterioles and capillaries. Extravasation of tumor cells was rare, and it seemed that the transmigrated cells were cleared quickly by the lung, leaving only the endothelium-attached cells as the seeds of secondary tumors. Early colonies were entirely within the blood vessels. Although most models of metastasis include an extravasation step early in the process, here we show that in the lung, metastasis is initiated by attachment of tumor cells to the vascular endothelium and that hematogenous metastasis originates from the proliferation of attached intravascular tumor cells rather than from extravasated ones. Intravascular metastasis formation would make early colonies especially vulnerable to intravascular drugs, and this possibility has potential for the prevention of tumor cell attachment to the endothelium.
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PMID:Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. 1061 33


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