Zebrafish models of rhabdomyosarcoma

Abstract

Rhabdomyosarcoma (RMS), an aggressive malignant neoplasm that shows features of skeletal muscle, is the most common soft tissue tumor of childhood. In children, the major subtypes are embryonal and alveolar. Although localized disease responds to a multimodal treatment, the prognosis for patients with high-risk features and metastasis remains dismal. Several in vivo models of RMS have been developed in mouse, human xenografts, zebrafish, and Drosophila to better understand the underlying mechanisms governing malignancy. The findings so far have indicated the potential role of skeletal muscle precursor cells in malignant transformation. To better understand histogenesis and different aspects of tumorigenesis in RMS, we have previously developed a robust zebrafish model of kRAS-induced RMS, which shares morphologic and immunophenotypic features with the human counterpart. Cross-species mircroarray comparisons confirm that conserved genetic pathways drive RMS growth. The ease for ex vivo manipulation allows the development of different transgenic and co-injection strategies to induce tumor formation in zebrafish. In contrast to other vertebrate model systems, the tumor onset in zebrafish is short, allowing for efficient study of different tumor processes including tumor growth, self-renewal, and maintenance.