Linked Life Data

18559512

Source:http://linkedlifedata.com/resource/pubmed/id/18559512

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-6-18
pubmed:abstractText
Cathepsin D (CD) up-regulation has been associated with human malignancy and poor prognosis. Thrombin up-regulated CD mRNA and protein in eight tumor cell lines as well as in human umbilical vascular endothelial cells (HUVEC). Thrombin increased the secretion of CD by 3- to 8-fold and enhanced chemotaxis ( approximately 2-fold) in 4T1 murine mammary CA cells, which was completely inhibited with the knockdown of CD. Secreted 4T1 CD induced neoangiogenesis by 2.4-fold on a chick chorioallantoic membrane, which was blocked in CD-KD cells. The addition of pure CD (2 ng) to the chick chorioallantoic membrane increased angiogenesis by 2.1-fold, which was completely inhibited by Pepstatin A (Pep A). CD enhanced human HUVEC chemotaxis and Matrigel tube formation by 2-fold, which was then blocked by Pep A. CD enhanced HUVEC matrix metalloproteinase 9 (MMP-9) activity by approximately 2-fold, which was completely inhibited by Pep A as well as a generic MMP inhibitor, GM6001. The injection of CD-KD 4T1 cells into syngeneic mice inhibited tumor growth by 3- to 4-fold compared with empty vector (EV) cells. Hirudin, a specific thrombin inhibitor, inhibited the growth of wild-type and EV cells by 2- to 3-fold, compatible with thrombin up-regulation of CD. CD and thrombin also contributed to spontaneous pulmonary metastasis; 4-fold nodule inhibition with CD versus EV and 4.6-fold inhibition with hirudin versus EV (P < 0.02). Thus, thrombin-induced CD contributes to the malignant phenotype by inducing tumor cell migration, nodule growth, metastasis, and angiogenesis. CD-induced angiogenesis requires the proteolytic activation of MMP-9.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4666-73
pubmed:meshHeading
pubmed-meshheading:18559512-Animals, pubmed-meshheading:18559512-Blotting, Western, pubmed-meshheading:18559512-Cathepsin D, pubmed-meshheading:18559512-Cell Movement, pubmed-meshheading:18559512-Cells, Cultured, pubmed-meshheading:18559512-Chemotaxis, pubmed-meshheading:18559512-Chick Embryo, pubmed-meshheading:18559512-Chorioallantoic Membrane, pubmed-meshheading:18559512-Endothelium, Vascular, pubmed-meshheading:18559512-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:18559512-Hirudins, pubmed-meshheading:18559512-Humans, pubmed-meshheading:18559512-Immunoprecipitation, pubmed-meshheading:18559512-Matrix Metalloproteinase 9, pubmed-meshheading:18559512-Mice, pubmed-meshheading:18559512-Mice, Inbred C57BL, pubmed-meshheading:18559512-Neoplasms, pubmed-meshheading:18559512-Neovascularization, Pathologic, pubmed-meshheading:18559512-Pepstatins, pubmed-meshheading:18559512-RNA, Messenger, pubmed-meshheading:18559512-RNA, Small Interfering, pubmed-meshheading:18559512-Thrombin, pubmed-meshheading:18559512-Umbilical Veins, pubmed-meshheading:18559512-Up-Regulation
pubmed:year
2008
pubmed:articleTitle
Thrombin up-regulates cathepsin D which enhances angiogenesis, growth, and metastasis.
pubmed:affiliation
Departments of Medicine and Radiation Oncology and Cell Biology, New York University School of Medicine, New York, New York.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural