Abstract
Background: The interaction of integrins and growth factor receptors in cells is tightly regulated, ensuring cell survival, proliferation, differentiation, adhesion, and migration. The IR generates reactive oxygen species, which leads to ECM remodeling and cell adhesion through the activation of proteases, soluble cytokines and growth factors. Integrins and adhesion of cells to ECM confer higher resistance to ionizing radiation and cytotoxic drug, a phenomenon known as cell adhesion mediated radiation resistance (CAM-RR) and cell adhesion mediated drug resistance (CAM-DR).Integrins’ involvement in CML progression is well appreciated through its survival, adhesion and migration signaling. The evaluation of global genetic response (in microarray) of ionizing radiation (IR) on integrins expression has not been attempted to specify theirrole and other cell adhesion molecules (CAMs) in CML. In this study, we have compared the microarray based CAMs response in myelogenous leukemia cells onIR exposure. Results: Results revealed differential regulation of many CAMs, with strongest expression of integrin β2 (CD18), whose role has not been fully appreciated in CML due to low level of expression. However, the synergistic LiCl(GSK3β inhibitor) and IR treatment significantly upregulates CD18 expression leading to enhanced survival, cell adhesion mediated drug/radiation resistance (CAM-DR/RR) and transcription of migration related genes. These effects could be undermined in the presence of CD18 antibody. This may be one of the reasons for CML resistance to radiation therapy and its relapse upon stem cell transplantation.Conclusion: This study proposes CD18 antagonist administration as an adjuvant in anti-CML therapy and other cancers in which it displays aberrant expression subsuming the contraindication of GSK3β inhibitor. Nevertheless, the CD18 mediated cell adhesion in tumor progression beckons development of improved drug regimensandidentification of diagnostic and prognostic signature for CML.