A team of researchers have developed a new animal model for rhabdomyoscarcoma (RMS), a deadly form of childhood muscle cancer. Scientists may have already succeeded in using the new zebrafish model to identify the group of cells that makes this form of cancer so resilient and dangerous.

RMS is diagnosed in more than 250 new patients each year in the US. Because of the aggressive nature of this kind of cancer, patients suffering from RMS must undergo an arduous treatment regime that often fails. Of those with metastatic disease at the time of diagnosis, less than 25% survive longer than five years.

Researchers have developed several murine models of RMS that have aided understanding of this disease, but these models require complicated mouse breeding and do not develop the necessary tumors quickly. To circumvent these problems, David M. Langenau and colleagues at the Children's Hospital Boston (MA) created a zebrafish model of embryonal RMS, the most common RMS subtype. By 80 days of age, half of the zebrafish develop embryonal RMS.

Langenau and his coworkers used microarray analysis and a technique called gene set enrichment analysis on the new model to find similarities in the gene expression profile of the zebrafish and human embryonal RMS cancer cells (Genes Dev., doi:10.1101/gad.1545007, published online 17 May). Their data strongly suggest that the molecular machinery responsible for embryonal RMS is conserved between the two species—evidence that the zebrafish will serve as a reliable model for the human disease.

In the same study, Langenau also took tumor cells from embryonal RMS zebrafish, sorted them by cell type, and transplanted them serially into healthy zebrafish. They found that a subset of tumors cells can recapitulate the cancer in healthy zebrafish, as though these cells are a kind of embryonal RMS 'stem cell'. The researchers noted that these tumor stem cells are similar in molecular composition to normal muscle satellite cells, a finding that suggests embryonal RMS may originate in muscle satellite cells.

“The ultimate goal [of the zebrafish model] would be to identify pathways that have gone understudied in RMS, ultimately leading to new ideas of how better to treat patients with this debilitating disease,” Langenau tells Lab Animal. He continues, “We are hopeful that further interrogation of the pathways we identified in our study will lead to new lines of treatment.”