Linked Life Data

12471616

Source:http://linkedlifedata.com/resource/pubmed/id/12471616

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-12-9
pubmed:abstractText
IL-8 is a strong chemoattractant for neutrophils, and it is constitutively produced by many tumors, including human melanomas. To determine the biologic importance of IL-8 for melanoma cells from primary and metastatic lesions, we transduced selected cell lines constitutively producing low levels of IL-8 with IL-8 cDNA using a replication-deficient adenoviral vector. Nontumorigenic SBcl2 primary melanoma cells formed tumors when transduced with increasing plaque-forming units of IL-8 per cell. However, at high IL-8 transduction levels (100 ng/ml/10(5) cells in 48 hr), tumor growth was impaired due to massive neutrophil infiltration. A similar biphasic response was observed in WM115 primary melanomas, which are tumorigenic but not metastatic. Depletion of neutrophils with an antibody that blocks the accumulation of granulocytes at the site of inflammation enabled transduced primary melanomas secreting high levels of IL-8 to survive and grow. In contrast, highly tumorigenic and metastatic 451Lu cells showed marked increases in tumor growth and number of metastatic foci in the lungs depending on the expression levels of IL-8. Cytotoxicity assays with isolated neutrophils confirmed the preferential killing of primary over metastatic melanoma cells. SBcl2 cells stimulated by IL-8 to form tumors in immunodeficient mice were induced to produce VEGF, suggesting that the angiogenic response is enhanced due to increased growth factor production. Our results demonstrate that nontumorigenic primary melanomas depend on IL-8 stimulation in vivo for growth and that tumor growth depends on the level of neutrophil infiltration. Metastatic melanomas proliferate in vivo independently of infiltrating neutrophils.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
335-43
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12471616-Adenoviridae, pubmed-meshheading:12471616-Animals, pubmed-meshheading:12471616-Chemotaxis, Leukocyte, pubmed-meshheading:12471616-Cytotoxicity, Immunologic, pubmed-meshheading:12471616-Disease Progression, pubmed-meshheading:12471616-Endothelial Growth Factors, pubmed-meshheading:12471616-Humans, pubmed-meshheading:12471616-Immunoenzyme Techniques, pubmed-meshheading:12471616-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:12471616-Interleukin-8, pubmed-meshheading:12471616-Lymphokines, pubmed-meshheading:12471616-Melanoma, pubmed-meshheading:12471616-Mice, pubmed-meshheading:12471616-Mice, Nude, pubmed-meshheading:12471616-Neutrophils, pubmed-meshheading:12471616-Skin Neoplasms, pubmed-meshheading:12471616-Transfection, pubmed-meshheading:12471616-Tumor Cells, Cultured, pubmed-meshheading:12471616-Vascular Endothelial Growth Factor A, pubmed-meshheading:12471616-Vascular Endothelial Growth Factors
pubmed:year
2003
pubmed:articleTitle
Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8.
pubmed:affiliation
The Wistar Institute, Philadelphia, PA 19104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't