Identification of CD44 as a Surface Biomarker for Drug Resistance by Surface Proteome Signature Technology

We developed Surface Proteome Signatures (SPS) for identification of new biomarkers playing a role in cancer drug resistance. SPS compares surface antigen expression of different cell lines by immunocytochemistry of a phage display antibody library directed to surface antigens of HT1080 fibrosarcoma cells. We applied SPS to compare the surface proteomes of two epithelially derived cancer cell lines, MCF7 and NCI/ADR-RES, which is drug resistant due to overexpression of the P-glycoprotein drug efflux pump. Surface proteome profiling identified CD44 as an additional biomarker that distinguishes between these two cell lines. CD44 immunohistochemistry can distinguish between tumors derived from these lines and predict tumor response to doxorubicin in vivo. We further show CD44 acts in drug resistance independently of P-glycoprotein in NCI/ADR-RES cells and increases expression of the anti-apoptotic protein Bcl-xL. Our findings illustrate the utility of SPS to distinguish between cancer cell lines and their derived tumors and identify novel biomarkers involved in drug resistance.