Abstract
The classical sacrococcygeal chordoma tumor presents with a typical morphology of lobulated myxoid tumor tissue with cords, strands and nests of tumor cells. The population of cells consists of small non-vacuolated cells, intermediate cells with a wide range of vacuolization and large heavily vacuolated (physaliferous) cells. To date analysis was only performed on bulk tumor mass because of its rare incidence, lack of suited model systems and technical limitations thereby neglecting its heterogeneous composition. We intended to clarify whether the observed cell types are derived from genetically distinct clones or represent different phenotypes. Furthermore, we aimed at elucidating the differences between small non-vacuolated and large physaliferous cells on the genomic and transcriptomic level. Phenotype-specific analyses of small non-vacuolated and large physaliferous cells in two independent chordoma cell lines yielded four candidate genes involved in chordoma cell development. UCHL3, coding for an ubiquitin hydrolase, was found to be over-expressed in the large physaliferous cell phenotype of MUG-Chor1 (18.7-fold) and U-CH1 (3.7-fold) cells. The mannosyltransferase ALG11 (695-fold) and the phosphatase subunit PPP2CB (18.6-fold) were found to be up-regulated in large physaliferous MUG-Chor1 cells showing a similar trend in U-CH1 cells. TMEM144, an orphan 10-transmembrane family receptor, yielded contradictory data as cDNA microarray analysis showed up- but RT-qPCR data down-regulation in large physaliferous MUG-Chor1 cells. Isolation of few but morphologically identical cells allowed us to overcome the limitations of bulk analysis in chordoma research. We identified the different chordoma cell phenotypes to be part of a developmental process and discovered new genes linked to chordoma cell development representing potential targets for further research in chordoma tumor biology.
Highlights
IntroductionArise within the bones of the axial skeleton and show a destructive growth, with a phenotype that recapitulates the notochord [1,2]
Chordomas are malignant tumors, arise within the bones of the axial skeleton and show a destructive growth, with a phenotype that recapitulates the notochord [1,2]
The phenotype with the highest proportion of cell divisions is the intermediate phenotype followed by the small non-vacuolated cells (59% vs. 40%, p,0.001) and large phenotype (59% vs. 34%, p,0.01)
Summary
Arise within the bones of the axial skeleton and show a destructive growth, with a phenotype that recapitulates the notochord [1,2]. Chordoma tumors are comprised of morphologically heterogeneous cells, i.e. ranging from smaller non-vacuolated spindly shaped cells to large cells with prominent vacuoles, usually referred to as ‘‘physaliferous cells’’ [3]. Within the range of these two phenotypes exists a continuum of intermediate cells with various degrees of vacuolization [3]. The underlying molecular mechanisms for this high degree of heterogeneity within chordoma tumors has not been investigated, holding great potential in revealing new drug targets. Chemoresistancy of chordoma tumors may be due to its heterogeneity, whereby the slow or non-dividing cells escape chemotherapeutic treatment [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
