Linked Life Data

20215425

Source:http://linkedlifedata.com/resource/pubmed/id/20215425

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-18
pubmed:abstractText
Chemokines influence tumor growth directly or indirectly via both angiogenesis and tumor-leukocyte interactions. Platelet factor-4 (CXCL4/PF-4), which is released from alpha-granules of activated platelets, is the first described angiostatic chemokine. Recently, it was found that the variant of CXCL4/PF-4 (CXCL4L1/PF-4var) could exert a more pronounced angiostatic and antitumoral effect than CXCL4/PF-4. However, the molecular mechanisms of the angiostatic activities of the PF-4 forms remain partially elusive. Here, we studied the biological properties of the chemically synthesized COOH-terminal peptides of CXCL4/PF-4 (CXCL4/PF-4(47-70)) and CXCL4L1/PF-4var (CXCL4L1/PF-4var(47-70)). Both PF-4 peptides lacked monocyte and lymphocyte chemotactic activity but equally well inhibited (25 nmol/L) endothelial cell motility and proliferation in the presence of a single stimulus (i.e., exogenous recombinant fibroblast growth factor-2). In contrast, when assayed in more complex angiogenesis test systems characterized by the presence of multiple mediators, including in vitro wound-healing (2.5 nmol/L versus 12.5 nmol/L), Matrigel (60 nmol/L versus 300 nmol/L), and chorioallantoic membrane assays, CXCL4L1/PF-4var(47-70) was found to be significantly (5-fold) more angiostatic than CXCL4/PF-4(47-70). In addition, low (7 microg total) doses of intratumoral CXCL4L1/PF-4var(47-70) inhibited B16 melanoma growth in mice more extensively than CXCL4/PF-4(47-70). This antitumoral activity was predominantly mediated through inhibition of angiogenesis (without affecting blood vessel stability) and induction of apoptosis, as evidenced by immunohistochemical and fluorescent staining of B16 tumor tissue. In conclusion, CXCL4L1/PF-4var(47-70) is a potent antitumoral and antiangiogenic peptide. These results may represent the basis for the design of CXCL4L1/PF-4var COOH-terminal-derived peptidomimetic anticancer drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1557-3125
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
322-34
pubmed:meshHeading
pubmed-meshheading:20215425-Angiostatic Proteins, pubmed-meshheading:20215425-Animals, pubmed-meshheading:20215425-Antineoplastic Agents, pubmed-meshheading:20215425-Biological Assay, pubmed-meshheading:20215425-Cell Line, Tumor, pubmed-meshheading:20215425-Cell Movement, pubmed-meshheading:20215425-Cell Proliferation, pubmed-meshheading:20215425-Cells, Cultured, pubmed-meshheading:20215425-Chick Embryo, pubmed-meshheading:20215425-Disease Models, Animal, pubmed-meshheading:20215425-Humans, pubmed-meshheading:20215425-Melanoma, Experimental, pubmed-meshheading:20215425-Mice, pubmed-meshheading:20215425-Mice, Inbred C57BL, pubmed-meshheading:20215425-Mice, Nude, pubmed-meshheading:20215425-Neovascularization, Pathologic, pubmed-meshheading:20215425-Peptide Fragments, pubmed-meshheading:20215425-Platelet Factor 4
pubmed:year
2010
pubmed:articleTitle
The COOH-terminal peptide of platelet factor-4 variant (CXCL4L1/PF-4var47-70) strongly inhibits angiogenesis and suppresses B16 melanoma growth in vivo.
pubmed:affiliation
Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't