Intercellular adhesion molecule-3 (ICAM-3) plays diverse roles in immune response and cancer. We generated NCI-H1299, a human non-small cell lung cancer cell (NSCLC), stably expressing ICAM-3, to examine whether ICAM-3 might affect cell migration or invasion in cancer. Cells stably transfected with ICAM-3 displayed upregulation of Akt activity resulting in an increase of cell migration and invasiveness, as well as upregulation of MMP-2 and -9. Treatment of transfected cells with a PI3 Kinase-specific inhibitor led to lower migration/invasiveness potential. Moreover, adenosine 3', 5'-monophosphate response element-binding protein(CREB), downstream component of the PI3 Kinase/Akt pathway was activated in the cells stably transfected with ICAM-3. CREB overexpression also showed increase of radio-resistance, cell proliferation, and migration/invasion, but CREB mutants - CREB133 and KCREB - did not show several effects of wild type CREB. Therefore, our data collectively suggest that activation of ICAM-3 stimulates increase of radio-resistance, proliferation, and migration/invasion through ICAM-3- PI3 Kinase/Akt -CREB pathway and CREB might have a role of mediator of several phenomena induced by ICAM-3.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2226.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO