title: Identification of CD44 as a surface biomarker for drug resistance by surface proteome signature technology.
abstract: 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 epithelial derived cancer cell lines, MCF7 and NCI/ADR-RES, which is drug resistant because of overexpression of the P-glycoprotein (P-gp) drug efflux pump. Surface proteomic 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 that CD44 plays a role in drug resistance, independently of P-gp, in NCI/ADR-RES cells and increases expression of the antiapoptotic 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.
authors.affiliation: Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
authors.forename: Jason W
authors.initials: JW
authors.lastname: Cain
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hauptschein
authors.forename: Jean K
authors.initials: JK
authors.lastname: Stewart
authors.forename: Tugba
authors.initials: T
authors.lastname: Bagci
authors.forename: Gary G
authors.initials: GG
authors.lastname: Sahagian
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Jay
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D020543:Proteome / Q000032:analysis* / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D020543:Proteome; D051020:bcl-X Protein; D004317:Doxorubicin