The
coxsackie-adenovirus receptor (CAR) is a developmentally regulated
intercellular adhesion molecule that was previously observed to be required for efficient
tumor formation. To confirm that observation, we compared the tumorigenicity of clonally derived test and control cell subsets that were genetically modified for CAR. Silencing CAR in
lung cancer cells with high constitutive expression reduced engraftment efficiency. Conversely, overexpressing CAR in
lung cancer cells with low constitutive expression did not affect
tumor formation or growth kinetics. A blocking antibody to the extracellular domain of CAR inhibited
tumor engraftment, implicating that domain as being important to this process. However, differences in adhesion properties attributable to this domain (barrier function and aggregation) could not be distinguished in the test groups in vitro, and the mechanisms underlying CAR's contribution to
tumor engraftment remain elusive. Because high CAR cells displayed a spindle-shaped morphology at baseline, we considered whether this expression was an accompaniment of other mesenchymal features in these
lung cancer cells. Molecular correlates of CAR were compared in model epithelial and mesenchymal type
lung cancer cells. CAR expression is associated with an absence of
E-cadherin, diminished expression of alpha- and
gamma-catenin, and increased Zeb1, Snail, and
vimentin expression in
lung cancer cells. In contrast, epithelial type (NCI-H292, Calu3)
lung cancer cells show comparatively low CAR expression. These data suggest that if the mesenchymal cell phenotype is an accurate measure of an undifferentiated and invasive state, then CAR expression may be more closely aligned with this phenotype of
lung cancer cells.