Genetic Modeling of Human Rhabdomyosarcoma
| Autor: | Christopher M. Counter, Stephen J. Qualman, Rex C. Bentley, Diane L. Downie, Corinne M. Linardic |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Cell type Pathology medicine.medical_specialty Adolescent Transplantation Heterologous Mice SCID Biology Malignancy Metastasis Mice Rhabdomyosarcoma medicine Animals Humans Myocyte Antigens Viral Tumor Muscle Skeletal Telomerase neoplasms Skeletal muscle Cancer Mesenchymal Stem Cells medicine.disease DNA-Binding Proteins Cell Transformation Neoplastic Genes ras medicine.anatomical_structure Oncology Sarcoma Neoplasm Transplantation |
| Zdroj: | Cancer Research. 65:4490-4495 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Rhabdomyosarcoma, a malignancy showing features of skeletal muscle differentiation, is the most common soft tissue sarcoma of childhood. The identification of distinct clinical presentation patterns, histologic tumor types, and risk groups suggests that rhabdomyosarcoma is a collection of highly related sarcomas rather than a single entity. In an effort to understand this seemingly heterogeneous malignancy, we constructed a genetically defined but malleable model of rhabdomyosarcoma by converting less differentiated human skeletal muscle cell precursors (SkMC) and committed human skeletal muscle myoblasts (HSMM) into their malignant counterparts by targeting pathways altered in rhabdomyosarcoma. Whereas the two cell types were both tumorigenic, SkMCs gave rise to highly heterogeneous tumors occasionally displaying features of rhabdomyosarcoma, whereas HSMMs formed rhabdomyosarcoma-like tumors with an embryonal morphology, capable of invasion and metastasis. Thus, despite introducing the same panel of genetic changes, altering the skeletal muscle cell of origin led to different tumor morphologies, suggesting that cell of origin may dictate rhabdomyosarcoma tumor histology. The ability to now genetically induce human rhabdomyosarcoma-like tumors provides a representative model to dissect the molecular mechanisms underlying this cancer. |
| Databáze: | OpenAIRE |
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