Profiling the cancer-prone microenvironment in a zebrafish model for MPNST

Microenvironmental contributions to soft tissue sarcoma progression are relatively undefined, particularly in the context of sarcoma onset. Use of animal models to reveal these contributions is impeded by (1) the difficulty in discriminating between microenvironmental, precancerous, and cancer cells; and (2) the challenge in defining a precancerous microenvironment. We developed a zebrafish model that allows segregation of microenvironmental, precancerous, and cancerous cell populations by fluorescence-activated cell sorting. This model exhibits high predilection for malignant peripheral nerve sheath tumor (MPNST), a type of soft tissue sarcoma that exhibits rapid, aggressive growth. Using RNA-seq, we profiled the transcriptomes of microenvironmental cells from our zebrafish MPNST model. We show broad activation of inflammatory and immune-associated signaling networks and significant upregulation of tumor-promoting ligands in both precancerous and cancerous microenvironments. We also identify specific ligand-receptor pairs that may promote sarcomagenesis. This work provides insight into how the microenvironment may promote MPNST initiation and progression. Overall design: N = 3-4 SAMPLES PER TREATMENT GROUP: Pre Cancerous Sox10 High Pre Cancerous Sox10 Low Control Sox10 Low Cancer Sox10 High Cancer Sox10 Low