Abstract

Abstract Circulating tumor cells (CTCs) are cells that have detached from the primary tumor and entered the bloodstream with the potential to seed metastatic tumors in distal sites. High CTC numbers correlate with aggressive disease, increased metastasis, and decreased time to relapse. It has also been shown that cancer stem cells (CSCs) represent a proportion of the CTCs present in patients. Given that CSCs are resistant to chemotherapy and are responsible for tumor initiation, it is posited that the CSCs are the seeds of metastasis. However, direct evidence for this hypothesis is limited due to the fact that there are few methods for culturing and studying these rare cells. We used a 3D culture chamber system (RealBio D4 ™) to establish long-term cultures of human-derived pancreatic tumors and to assess the effect of gemcitabine treatment on the CSC population of these cultures. We observed that the system's 3D matrix supported culture development and incorporation of tissue organization and microenvironment. The chamber design allowed CTCs generated within the cultures to migrate out of the cell mass into the circulating nutrient medium where they were collected for characterization. Further, tumor tissue grown on the matrix showed an enrichment of CSCs after gemcitabine treatment analogous to the enrichment observed in vivo. Future studies will focus on characterizing isolated CTCs and circulating CSCs from pancreas and breast cancer models, determine their response to therapy, and elucidate the relationship of different CTC populations on tumor spread. Ultimately, these studies may support the use of CTCs and circulating CSCs as biomarkers in clinical trials. Citation Format: Marina C. Cabrera, Elaine Hurte. Establishing long-term circulating tumor cells (CTCs) in a 3D culture system in vitro. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1524. doi:10.1158/1538-7445.AM2015-1524

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