Linked Life Data

7686887

Source:http://linkedlifedata.com/resource/pubmed/id/7686887

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1993-8-12
pubmed:abstractText
Initial arrest of tumor cells in the microvasculature and their attachment to the endothelium and subendothelial matrix (SEM) are essential prerequisites for metastasis to occur. Factors mediating these interactions are viewed as important determinants of the tumor-cell metastatic phenotype. In this work we have studied the effects of thrombin, its analogs and its precursors on the adhesive properties and metastatic potential of tumor cells. We show that alpha-thrombin, the native form of the key coagulation enzyme, is capable of enhancing tumor-cell adhesion to both the endothelium and SEM components represented by fibronectin. Subclotting, physiological concentrations of alpha-thrombin produced a 2- to 5-fold increase in tumor-cell adhesion. A bell-shaped dose-response curve was observed, with maximal effect at 0.1 U/ml. Maximum effect occurred when cells were exposed to the agonist for 15 min and exposure for up to 4 hr resulted in enhanced tumor-cell adhesion. Prolonged incubation with thrombin resulted in a decline in the thrombin-enhanced adhesion which reached unstimulated control levels by 24 hr. Thrombin precursors and active-site-inhibited thrombin analogs only had minimal adhesion-enhancing activity; nitro- and exosite-alpha-thrombin, which retain a functional active site, mimicked, although to a lesser degree, the action of alpha-thrombin. Tumor-cell incubation with thrombin resulted in an upregulated cell-surface expression of the alpha11b beta 3 integrin, a receptor mediating interactions between tumor cells and endothelial cells, and between tumor cells and SEM. Antibodies against alpha 11b beta 3 integrin effectively inhibited thrombin-enhanced tumor-cell adhesion. Thrombin effects on tumor cells involved the PKC signal transduction pathway as thrombin-enhanced adhesion was inhibited by pre-incubation with PKC inhibitors and a transient PKC translocation from cytosol to membrane was observed following thrombin challenge. In vivo, thrombin-treated tumor cells demonstrated a 2-fold increase in their lung-colonizing ability. In contrast to the adhesion results, the metastasis-enhancing effects of alpha-thrombin were mimicked by a thrombin precursor (prothrombin) and thrombin analogs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
793-806
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:7686887-Animals, pubmed-meshheading:7686887-Antibodies, Monoclonal, pubmed-meshheading:7686887-Blood Coagulation, pubmed-meshheading:7686887-Carcinosarcoma, pubmed-meshheading:7686887-Cell Adhesion, pubmed-meshheading:7686887-Dose-Response Relationship, Drug, pubmed-meshheading:7686887-Fibronectins, pubmed-meshheading:7686887-Flow Cytometry, pubmed-meshheading:7686887-Humans, pubmed-meshheading:7686887-Integrins, pubmed-meshheading:7686887-Lung Neoplasms, pubmed-meshheading:7686887-Melanoma, Experimental, pubmed-meshheading:7686887-Neoplasm Metastasis, pubmed-meshheading:7686887-Platelet Glycoprotein GPIIb-IIIa Complex, pubmed-meshheading:7686887-Protein Kinase C, pubmed-meshheading:7686887-Rats, pubmed-meshheading:7686887-Thrombin, pubmed-meshheading:7686887-Tumor Cells, Cultured
pubmed:year
1993
pubmed:articleTitle
Thrombin increases the metastatic potential of tumor cells.
pubmed:affiliation
Department of Radiation Oncology, Wayne State University, Detroit, MI.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't