Abstract 5769: Modeling the tumor invasion front using 3D fluidic tumoroid culture of cancer cells

Abstract

Abstract To realize the promise of precision medicine, it is important to integrate phenotypic assessment of cell populations to genomic data. The analysis of invading leader cells at the tumor invasion front is of interest as they may be guided by a targetable molecular phenotype. However, there is a lack of suitable platforms on which to analyze the tumor invasion front. In this study, we have designed and constructed a fluidic device for long-term (several days to weeks) 3-dimensional tumoroid culture of diverse cancer cells. Using this device, we can recapitulate the tumor invasion front and at the same time quantify the invasive potential of different breast cancer cell line models. Analyses of the tumor invasion front indicated a region of higher proliferation and suggest that the leader cells possess a different molecular phenotype from the tumoroid mass. Interestingly, significant heterogeneity among invading cells was still observed, suggesting that there could be: 1) the presence of multiple subpopulations of invasive cells, each with a different clonal genetic signature; and/or 2) reversible phenotypic switching occurring among invading cells due to phenotypic plasticity. These results obtained using this innovative device highlight and present a promising solution to the challenges developing adequate therapeutics accounting for tumor phenotypic heterogeneity. There is potential for the device for use in personalized medicine at diagnosis, allowing for both the quantification of disease progression risk as well as the molecular characterization of the invasive subpopulations from patient samples and their response to tailored therapies. Citation Format: Koh Meng Aw Yong, Christopher Oliver, Megan Altemus, Zhi Fen Wu, Sofia Merajver. Modeling the tumor invasion front using 3D fluidic tumoroid culture of cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5769. doi:10.1158/1538-7445.AM2017-5769