Linked Life Data

20679910

Source:http://linkedlifedata.com/resource/pubmed/id/20679910

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-9-9
pubmed:abstractText
Melanoma is the most lethal skin tumor in large part because of a propensity for early metastasis. Good models of this most clinically relevant feature of melanoma are lacking. Here, we report the development of an in-vivo model of metastasis that relies on orthotopic injection of green fluorescent protein-tagged lines in immunodeficient mice, serial intravital imaging of tumor progression, and quantification of distant spread by two-photon laser scanning microscopy, immunohistochemistry, and real-time PCR analysis. Using this system, we report an assessment of the in-vivo growth and metastatic properties of 11 well-characterized human melanoma cell lines. A subset of lines showed rapid in-vivo growth with invasion of host vasculature and distant seeding of viscera in this system. The ability to form metastasis in vivo did not correlate with three-dimensional collagen invasion in vitro. Surprisingly, similar lines in terms of molecular genetic events differed markedly in their propensity to metastasize to distant organs such as brain and lung. In particular, two lines harboring B-RAF mutation and high levels of phosphorylated ERK and AKT were reproducibly unable to form tumors after orthotopic injection. Similarly, two previously identified RAS/RAF wildtype 'epithelial like' lines that do not have elevated phosphorylated ERK and AKT or express TWIST1 mRNA still showed a pronounced ability for orthotopic growth and metastatic spread. All the metastatic cell lines in this model showed increased NEDD9 expression, but NEDD9 lentiviral overexpression did not convey a metastatic phenotype on nonmetastatic cells. These data suggest that melanoma metastasis is a molecularly heterogeneous process that may not require epithelial-to-mesenchymal transition or ERK activation, although both may facilitate the process.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1473-5636
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
361-71
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed-meshheading:20679910-Adaptor Proteins, Signal Transducing, pubmed-meshheading:20679910-Animals, pubmed-meshheading:20679910-Cell Line, Tumor, pubmed-meshheading:20679910-Female, pubmed-meshheading:20679910-Genes, ras, pubmed-meshheading:20679910-Humans, pubmed-meshheading:20679910-Melanoma, pubmed-meshheading:20679910-Mice, pubmed-meshheading:20679910-Mice, Inbred NOD, pubmed-meshheading:20679910-Mice, SCID, pubmed-meshheading:20679910-Mutation, pubmed-meshheading:20679910-Neoplasm Metastasis, pubmed-meshheading:20679910-Neoplasm Transplantation, pubmed-meshheading:20679910-Neoplasms, Experimental, pubmed-meshheading:20679910-Skin Neoplasms, pubmed-meshheading:20679910-Transplantation, Heterologous, pubmed-meshheading:20679910-Transplantation, Heterotopic, pubmed-meshheading:20679910-raf Kinases
pubmed:year
2010
pubmed:articleTitle
Metastasis in an orthotopic murine model of melanoma is independent of RAS/RAF mutation.
pubmed:affiliation
Departments of Medicine and Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural