Mouse model showed that timing of protein expression is linked to cancer formation.

A novel mouse model for synovial sarcoma enabled scientists to discover unkown connections between SYT-SSX, a chimeric fusion protein, and the cancer. The study also provides new information about the timing and environment required for initiation and progression of synovial sarcoma.

Mario R. Capecchi, Ph.D., from the Howard Hughes Medical Institute and the department of human genetics at the University of Utah School of Medicine, and colleagues developed a mouse model that expresses human SYT-SSX in chosen target cells. Using this approach, the researchers discovered that although synovial sarcoma is named for its common proximity to limb joints, this tumor appears to arise from skeletal muscle precursor cells called myoblasts. Expression of SYT-SSX in myoblasts was sufficient to induce synovial sarcoma in 100% of mice.

The researchers also controlled the timing of fusion protein expression so as to examine what happens when the protein is expressed at different stages of muscle development. Earlier expression of SYT-SSX disrupted normal development and was associated with embryonic lethality while expression in more differentiated muscle cells induced significant muscle cell damage and death in the absence of tumor formation.

Further studies demonstrated that this mouse model of synovial sarcoma faithfully recapitulates human synovial sarcoma on multiple levels. As in the human cancer, tumors in the mice arise most commonly in close proximity to joints. The researchers speculate that the cartilage associated with joints may contribute to a favorable microenvironment for the SYT-SSX-expressing cells.

The research will appear in the April issue of Cancer Cell.

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