Animal models of soft-tissue sarcoma

Abstract

Soft-tissue sarcomas (STSs) are rare mesenchymal tumors that arise from muscle, fat and connective tissue. Currently, over 75 subtypes of STS are recognized. The rarity and heterogeneity of patient samples complicate clinical investigations into sarcoma biology. Model organisms might provide traction to our understanding and treatment of the disease. Over the past 10 years, many successful animal models of STS have been developed, primarily genetically engineered mice and zebrafish. These models are useful for studying the relevant oncogenes, signaling pathways and other cell changes involved in generating STSs. Recently, these model systems have become preclinical platforms in which to evaluate new drugs and treatment regimens. Thus, animal models are useful surrogates for understanding STS disease susceptibility and pathogenesis as well as for testing potential therapeutic strategies.

Fig. 1.

Gene activation or deletion by Cre recombinase. Cre recombinase deletes DNA that is flanked by loxP sites. (A) Fusion-gene activation by tissue-specific Cre. Removal of a silenced STOP cassette by Cre allows for expression of the Pax3-Fkhr fusion gene (Keller et al., 2004b). (B) Gene activation by CreER activity. Addition of tamoxifen activates CreER, allowing for removal of the silenced loxP-STOP-loxP cassette. This results in expression of the oncogene SYT-SSX2 (Haldar et al., 2007). (C) Gene deletion via Cre recombinase. Cre activity removes the p53 gene flanked by two loxP sites (Jonkers et al., 2001).