Sarcomas constitute a high percentage (∼13%) of cancer-related deaths among pediatric patients between 0-19 years of age, with Rhabdomyosarcoma (RMS) being the most common pediatric soft tissue sarcoma and Ewing Sarcoma being the second most common malignant bone tumor in children. Yet, survival for those who develop such metastatic sarcomas remains below 20-30%. Interestingly, SOX family proteins are known to be up regulated in various cancer types and play a role in cancer progression (tumorigenesis, metastasis, etc.). More specifically, targeted knockdown of SOX18 has been shown to suppress various tumorigenic properties in cancer cell lines including osteosarcoma cells, hepatocellular carcinoma cells and breast cancer cells. Additionally, prior studies showed inhibition of IGFR leads to compensatory pathway activation via other RTK receptors resulting in continued cell survival. Upregulation of SOX18 was observed in such cases. Thus, it is important to clarify the role of SOX18 in RMS and ES. Ewing Sarcoma (ES8) cell line was infected with shSOX18 to produce knockdown and selected via puromycin resistance. Cell migration, cell proliferation and colony formation assays were used to characterize effects of knockdown. Results showed that the shRNA was effective in SOX18 knockdown and lead to reduced cell proliferation in ES8 cells. Further evaluation of knockdown effects on angiogenesis will be analyzed using chick chorioallantoic membrane (CAM) assays. We anticipate characterization of the role of SOX18 in RMS and ES may inform future development of novel targeted treatments and increased understanding of role of SOX18 in activation of RTK compensatory pathways during IGFR inhibition in pediatric sarcomas.
Rubannelsonkumar, Cherubina, "Role of SOX18 in Promoting Tumorigenesis in Pediatric Cancer Cell Lines" (2022). St. Mary's University Honors Theses and Projects. 10.
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