Chondrosarcoma is a malignant bone tumor that accounts for approximately 25% of all bone neoplasms. The“Cancer Stem Cell” (CSC) hypothesis states that tumor contains a cell subpopulation with stemness features. Spherecultures are routinely used for self-renewal assays and to select CSCs. Our purpose was to investigate the geneprofile of chondrospheres and identify target genes for chondrosarcoma treatment. Whole-genome microarray wasused to compare the gene expression of floating spheres with that of adherent counterparts derived from a humanprimary chondrosarcoma. In addition, CD133, OCT4, SOX2, and collagen type II markers were tested both withReal-Time PCR and flow cytometry, and cell cycle analysis and resistance to cisplatin treatment were performed.Microarray analyses revealed that 1405 genes were found differentially expressed, of which 629 genes were upregulatedand 776 down-regulated in chondrospheres, with a 2-fold cut-off threshold. Restricting analyses with a3-fold cut-off threshold, the number of up-regulated and down-regulated probes was 251 and 302, respectively. Themost highly up-regulated genes were involved in stemness, multidrug resistance, cell cycle, apoptosis regulation,migration, motility, and invasion. Furthermore, chondrospheres expressed CD133, OCT3/4, and SOX2, and showeda remarkable resistance to cisplatin-induced apoptosis compared with their adherent counterpart. In conclusion,this study highlights that: (i) the molecular profile of chondrospheres identifies genes that are potential targets forchondrosarcoma treatment and (ii) chondrospheres are strongly resistant to cisplatin treatment.
Molecular Profiling of Human Primary Chondrosarcoma-Derived Spheres Reveals Specific and Target Genes Involved in Multidrug Resistance and Metastasis
LA Noce M;
2013-01-01
Abstract
Chondrosarcoma is a malignant bone tumor that accounts for approximately 25% of all bone neoplasms. The“Cancer Stem Cell” (CSC) hypothesis states that tumor contains a cell subpopulation with stemness features. Spherecultures are routinely used for self-renewal assays and to select CSCs. Our purpose was to investigate the geneprofile of chondrospheres and identify target genes for chondrosarcoma treatment. Whole-genome microarray wasused to compare the gene expression of floating spheres with that of adherent counterparts derived from a humanprimary chondrosarcoma. In addition, CD133, OCT4, SOX2, and collagen type II markers were tested both withReal-Time PCR and flow cytometry, and cell cycle analysis and resistance to cisplatin treatment were performed.Microarray analyses revealed that 1405 genes were found differentially expressed, of which 629 genes were upregulatedand 776 down-regulated in chondrospheres, with a 2-fold cut-off threshold. Restricting analyses with a3-fold cut-off threshold, the number of up-regulated and down-regulated probes was 251 and 302, respectively. Themost highly up-regulated genes were involved in stemness, multidrug resistance, cell cycle, apoptosis regulation,migration, motility, and invasion. Furthermore, chondrospheres expressed CD133, OCT3/4, and SOX2, and showeda remarkable resistance to cisplatin-induced apoptosis compared with their adherent counterpart. In conclusion,this study highlights that: (i) the molecular profile of chondrospheres identifies genes that are potential targets forchondrosarcoma treatment and (ii) chondrospheres are strongly resistant to cisplatin treatment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
