Linked Life Data

20453887

Source:http://linkedlifedata.com/resource/pubmed/id/20453887

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2010-7-2
pubmed:abstractText
ADAMs (a disintegrin and metalloprotease) are transmembrane proteins involved in a variety of physiological processes and tumorigenesis. Recently, ADAM8 has been associated with poor prognosis of lung cancer. However, its contribution to tumorigenesis in the context of lung cancer metastasis remains unknown. Native ADAM8 expression levels were lower in lung cancer cell lines. In contrast, we identified and characterized two novel spliced isoforms encoding truncated proteins, Delta18a and Delta14', which were present in several tumor cell lines and not in normal cells. Overexpression of Delta18a protein resulted in enhanced invasive activity in vitro. ADAM8 and its Delta14' isoform expression levels were markedly increased in lung cancer cells, in conditions mimicking tumor microenvironment. Moreover, addition of supernatants from Delta14'-overexpressing cells resulted in a significant increase in tartrate-resistant acid phosphatase+ cells in osteoclast cultures in vitro. These findings were associated with increased pro-osteoclastogenic cytokines interleukin (IL)-8 and IL-6 protein levels. Furthermore, lung cancer cells overexpressing Delta14' increased prometastatic activity with a high tumor burden and increased osteolysis in a murine model of bone metastasis. Thus, the expression of truncated forms of ADAM8 by the lung cancer cells may result in the specific upregulation of their invasive and osteoclastogenic activities in the bone microenvironment. These findings suggest a novel mechanism of tumor-induced osteolysis in metastatic bone colonization.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3758-69
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer.
pubmed:affiliation
Adhesion and Metastasis Laboratory, Division of Oncology, Center for Applied Biomedical Research (CIMA), University of Navarra, Pamplona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't