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Resolving tumor heterogeneity: genes involved in chordoma cell development identified by low-template analysis of morphologically distinct cells.

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.

SUBMITTER: El-Heliebi A

PROVIDER: S-EPMC3913634 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Resolving tumor heterogeneity: genes involved in chordoma cell development identified by low-template analysis of morphologically distinct cells.

El-Heliebi Amin A Kroneis Thomas T Wagner Karin K Meditz Katharina K Kolb Dagmar D Feichtinger Julia J Thallinger Gerhard G GG Quehenberger Franz F Liegl-Atzwanger Bernadette B Rinner Beate B

PloS one 20140204 2

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 heteroge ...[more]

PMID: 24503940

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Project description:BackgroundCamponotus floridanus ant colonies are comprised of a single reproductive queen and thousands of sterile female offspring that consist of two morphologically distinct castes: smaller minors and larger majors. Minors perform most of the tasks within the colony, including brood care and food collection, whereas majors have fewer clear roles and have been hypothesized to act as a specialized solider caste associated with colony defense. The allocation of workers to these different tasks depends, in part, on the detection and processing of local information including pheromones and other chemical blends such as cuticular hydrocarbons. However, the role peripheral olfactory sensitivity plays in establishing and maintaining morphologically distinct worker castes and their associated behaviors remains largely unexplored.ResultsWe examined the electrophysiological responses to general odorants, cuticular extracts, and a trail pheromone in adult minor and major C. floridanus workers, revealing that the repertoire of social behaviors is positively correlated with olfactory sensitivity. Minors in particular display primarily excitatory responses to olfactory stimuli, whereas major workers primarily manifest suppressed, sub-solvent responses. The notable exception to this paradigm is that both minors and majors display robust, dose-dependent excitatory responses to conspecific, non-nestmate cuticular extracts. Moreover, while both minors and majors actively aggress non-nestmate foes, the larger and physiologically distinct majors display significantly enhanced capabilities to rapidly subdue and kill their adversaries.ConclusionsOur studies reveal the behavioral repertoire of minors and majors aligns with profound shifts in peripheral olfactory sensitivity and odor coding. The data reported here support the hypothesis that minors are multipotential workers with broad excitatory sensitivity, and majors are dedicated soldiers with a highly specialized olfactory system for distinguishing non-nestmate foes. Overall, we conclude that C. floridanus majors do indeed represent a physiologically and behaviorally specialized soldier caste in which caste-specific olfactory sensitivity plays an important role in task allocation and the regulation of social behavior in ant colonies.

Dataset Information

Resolving tumor heterogeneity: genes involved in chordoma cell development identified by low-template analysis of morphologically distinct cells.

Publications

Resolving tumor heterogeneity: genes involved in chordoma cell development identified by low-template analysis of morphologically distinct cells.

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