title: Quantitative proteomic analysis of tumor reversion in multiple myeloma cells.
abstract: Tumor reversion is defined as the process by which cancer cells lose their malignant phenotype. However, relatively little is known about the cellular proteome changes that occur during the reversion process. A biological model of multiple myeloma (MM) reversion was established by using the H-1 parvovirus as a tool to select for revertant cells from MM cells. Isolated revertant cells displayed a strongly suppressed malignant phenotype both in vitro and in vivo. To explore possible mechanisms of MM reversion, the protein profiles of the revertant and parental MM cells were compared using a quantitative proteomic strategy termed SILAC-MS. Our results revealed that 379 proteins were either activated or inhibited during the reversion process, with a much greater proportion of the proteins, including STAT3, TCTP, CDC2, BAG2, and PCNA, being inhibited. Of these, STAT3, which is significantly down regulated, was selected for further functional studies. Inhibition of STAT3 expression by RNA interference resulted in suppression of the malignant phenotype and concomitant down regulation of TCTP expression, suggesting that myeloma reversion operates, at least in part, through inhibition of STAT3. Our results provide novel insights into the mechanisms of tumor reversion and suggest new alternative approaches for MM treatment.
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China. gefeng@ihb.ac.cn
authors.forename: Feng
authors.initials: F
authors.lastname: Ge
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Sheng-Ce
authors.initials: SC
authors.lastname: Tao
authors.forename: Kaio
authors.initials: K
authors.lastname: Kitazato
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Xian-En
authors.initials: XE
authors.lastname: Zhang
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Bi
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D045744:Cell Line, Tumor; D052661:H-1 parvovirus; D006801:Humans; D007553:Isotope Labeling; D009101:Multiple Myeloma / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000032:analysis* / Q000378:metabolism; D009385:Neoplastic Processes; D010641:Phenotype; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D034622:RNA Interference; D050796:STAT3 Transcription Factor; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1