1. ¹Department of Surgery, Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
2. ²Division of Pulmonary and Critical Care Medicine, Department of Medicine, Research/Development, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA, USA
3. ³Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA

Correspondence: Dr RK Batra, MD, Geffen School of Medicine at UCLA and Division of Pulmonary and Critical Care Medicine, Veterans Administration Greater Los Angeles Health Care System, 11301 Wilshire Blvd 111Q, Los Angeles, CA 90073, USA. E-mail: rbatra@ucla.edu

Received 13 January 2009; Revised 11 March 2009; Accepted 9 April 2009; Published online 8 June 2009.

Abstract

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 - and -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.