Abstract 3714: Efficient derivation and expansion of tumor cell lines from primary and xenotransplanted pancreatic, ovarian and renal tumors

Abstract

Cancer cell lines are widely used as in vitro models to study tumor biology and for efficacy testing of novel anti-cancer therapeutics. In the past, most of this work has been done using established cell lines that have been cultured for decades. Extensive in vitro propagation has been shown to lead to the acquisition of multiple genetic and epigenetic alterations in cell lines, leading to decreased heterogeneity and the lack of tumor initiating as well as multi-lineage differentiation capacity. Consequently, established cell lines only insufficiently resemble the characteristics of tumors and thus have limited applicability as in vitro models for example. To overcome this hurdles, cell lines can be derived from primary cancer biopsies. However, this process is very inefficient for most tumor entities. In addition, most of the media used include largely undefined serum, such as FBS, which has been shown to drive primary tumor cell cultures to a more differentiated state when used over multiple passages. We have developed advanced, serum-free media for derivation and expansion of tumor cell lines from pancreatic, ovarian or renal tumors. Our media have been optimized concerning formulation, stability, and usability and allow for efficient generation of primary cell lines from both, patient and xenotransplanted tumors. Primary cell lines derived with our media retained their tumorigenic potential and could therefore be xenotransplanted and propagated in immunodeficient mice. Notably, the resulting tumors closely resembled the initial patient tumor as shown on the histomorphological as well as functional level. Moreover, the primary cell lines closely resembled essential characteristics of the parental tumor in vitro, including expression of subtype-specific markers, cellular heterogeneity, as well as genetic and epigenetic signatures. Taken together, we have developed serum-free medium for efficient derivation and expansion of tumor cell lines from primary and xenotransplanted pancreatic, ovarian and renal tumors, allowing for the establishment of easily accessible in vitro as well as corresponding xenografting vivo models. This facilitates the translation of in vitro findings directly into in vivo settings, allowing for more reliable pre-clinical modelling. Citation Format: Olaf Hardt, David Agorku, Anne Langhammer, Franziska Zickgraf, Felix Geist, Elisa M. Noll, Christian Eisen, Andreas Bosio, Martin R. Sprick, Andreas Trumpp. Efficient derivation and expansion of tumor cell lines from primary and xenotransplanted pancreatic, ovarian and renal tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3714.