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Human organotypic cancer model

: Konzok, Sebastian; Schindler, Susann; Braun, Armin; Sewald, Katherina

ALTEX Proceedings 3 (2014), No.1, pp.214, Abstract VI-1-571
ISSN: 2194-0479
World Congress on Alternatives and Animal Use in the Life Sciences <9, 2014, Prag>
Fraunhofer ITEM ()

Multiple xenocraft mouse models have been generated to understand cancer, with the disadvantages of less predictive, expensive or technically complicated procedures. Here we present an innovative ex vivo organotypic tumor invasion model using living human precision-cut lung slices (PCLS) and cancer cells.
An AdGFP transduced human breast cancer cell line MDA MB 231 was added to human PCLS over a period of one week. Viability assays show intact human tissue during the infection with the cancer cells. Growth curves and Ki67 staining reflect proliferation of cancer cells over the observation period time in human PCLS. Immune response and neoangiogenesis were determined by the cytokine markers VEGF, IL 10, IL 1beta and GM CSF. The decrease of the proinflammatory cytokine IL 1beta was linked to the number of MDA MB 231 associated macrophages in human PCLS. The model mimics cancer cell proliferation in the microenvironment of human tissue without using artificial substances. It provides the possibility to gain insights into functional local immune responses with human physiology background. The model can be adjusted to other cancer targeted organs. In terms of the 3R concept, this alternative model does not require any animal experiments and takes advantage of human tissue.