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Murine precision-cut liver slices (PCLS): A new tool for studying tumor microenvironments and cell signaling ex vivo

: Koch, Alexandra; Saran, Shashank; Tran, Doan Duy Hai; Klebba-Färber, Sabine; Thiesler, Hauke; Sewald, Katherina; Schindler, Susann; Braun, Armin; Klopfleisch, Robert; Tamura, Teruko

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Cell communication and signaling 12 (2014), Art. 73, 13 pp.
ISSN: 1478-811X
Journal Article, Electronic Publication
Fraunhofer ITEM ()
precision-cut liver slices (PCLS); Perfuorochemicals; communication between cancer and liver-resident cells; IMARIS image analysis program; THOC5 knockout liver

Background: One of the most insidious characteristics of cancer is its spread to and ability to compromise distant organs via the complex process of metastasis. Communication between cancer cells and organ-resident cells via cytokines/chemokines and direct cell-cell contacts are key steps for survival, proliferation and invasion of metastasized cancer cells in organs. Precision-cut liver slices (PCLS) are considered to closely reflect the in vivo situation and are potentially useful for studying the interaction of cancer cells with liver-resident cells as well as being a potentially useful tool for screening anti-cancer reagents. Application of the PCLS technique in the field of cancer research however, has not yet been well developed. Results: We established the mouse PCLS system using perfluorodecalin (PFD) as an artificial oxygen carrier. Using this system we show that the adherence of green fluorescent protein (GFP) labeled MDA-MB-231 (highly invasive) cells to liver tissue in the PCLS was 5-fold greater than that of SK-BR-3 (less invasive) cells. In addition, we generated PCLS from THOC5, a member of transcription/export complex (TREX), knockout (KO) mice. The PCLS still expressed Gapdh or Albumin mRNAs at normal levels, while several chemokine/growth factor or metalloprotease genes, such as Cxcl12, Pdgfa, Tgfb, Wnt11, and Mmp1a genes were downregulated more than 2-fold. Interestingly, adhesion of cancer cells to THOC5 KO liver slices was far less (greater than 80% reduction) than to wild-type liver slices. Conclusion: Mouse PCLS cultures in the presence of PFD may serve as a useful tool for screening local adherence and invasiveness of individual cancer cells, since single cells can be observed. This method may also prove useful for identification of genes in liver-resident cells that support cancer invasion by using PCLS from transgenic liver.