Abstract B37: Detection of sarcoma circulating tumor cells using a size based microfiltration device

The inability to effectively treat hematogenous metastasis remains the largest challenge of sarcoma therapy. The ability to isolate, quantify, and study circulating tumor cells (CTC) in sarcomas has the potential to enhance our understanding of the biology of metastasis, altering the way we treat patients with high grade sarcomas. Using a size based filtration device, CellSieve™, we were able to successfully identify and quantify CTC in a metastatic xenograft model as well as in blood samples from patients with high grade sarcomas. In mice, we utilized our orthotopic implantation/amputation model of metastasis. Using a TdTomato-expressing Ewing sarcoma cell line and a cocktail of fluorescently labeled antibodies to vimentin and CD45, we were able to detect both CTC and circulating tumor clusters (CTCL) in mice with growing tumors and with metastatic disease, but not in mice immediately post-amputation. These experiments were augmented with samples collected from patients with high grade sarcomas. In 18 samples from 15 patients, we were able to identify both CTC and CTCL. Furthermore, we were also able to validate the presence of CTC by PCR amplification of sarcoma-associated chromosomal translocations. Future work will use this system to explore the biology of sarcoma metastasis by studying genetic, transcriptional, and epigenetic characteristics of CTC and CTCL and comparing these cells to those in the bulk primary tumor. We will also further explore the possibility that CTC and/or CTCL might serve as a biomarker of disease burden, response to treatment, or metastatic risk. Citation Format: Masanori Hayashi, Peixuan Zhu, Catherine M. Albert, Diana Steppan, Gregory McCarty, Kyle W. Jackson, Cha-Mei Tang, David M. Loeb. Detection of sarcoma circulating tumor cells using a size based microfiltration device. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B37.