Depósito Académico >
Facultad de Ciencias >
Departamento de Histología y Anatomía Patológica >
DA - Ciencias - HAP - Artículos de revista >
|Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer|
|Authors: ||Hernandez, I. (I.)|
Moreno, J.L. (José Luis)
Zandueta, C. (Carolina)
Montuenga, L.M. (Luis M.)
Lecanda, F. (Fernando)
|Issue Date: ||1-Jul-2010|
|Publisher: ||Nature Publishing Group|
|Publisher version: ||http://dx.doi.org/10.1038/onc.2010.130|
|Citation: ||Hernandez I, Moreno JL, Zandueta C, Montuenga L, Lecanda F. Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer. Oncogene 2010 Jul 1;29(26):3758-3769.|
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, D18a and
D140, which were present in several tumor cell lines and not
in normal cells. Overexpression of D18a protein resulted in
enhanced invasive activity in vitro. ADAM8 and its D140
isoform expression levels were markedly increased in lung
cancer cells, in conditions mimicking tumor microenvironment.
Moreover, addition of supernatants from D140-overexpressing
cells resulted in a significant increase in tartrate-resistant acid
phosphataseþ 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 D140 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.
|Permanent link: ||http://hdl.handle.net/10171/13050|
|Appears in Collections:||DA - CIMA - Oncología - Adhesión y metástasis - Artículos de revista|
DA - CIMA - Oncología - Biomarcadores - Artículos de Revista
DA - Ciencias - HAP - Artículos de revista
|Files in This Item:|
There are no files associated with this item.
Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.