Core 2: PDX Tumor Core

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ABSTRACT (PATIENT-DERIVED XENOGRAFT CORE) The Patient-Derived Xenograft (PDX) Core will support the efforts of the Chicago Region-PSOC to define the role of the spatio-temporal organization of chromatin in information transfer in cancer by providing CR-PSOC investigators with a valuable model of human cancer that will enable investigators to extend their observations to actual patient tumor cells. The Core will create and maintain carefully delineated, in vivo human tumor models from a broad range of histologies that retain the characteristics of fresh human tumors. These PDX models are passaged continuously in vivo and are never exposed to tissue culture plastic and the limitations imposed by tissue culture selection of certain tumor cell clones. The PDX tumors retain histological characteristics that are similar to the patient tumors from which they were derived. Thus, these models are thought to be closer to the clinical situation than traditional xenograft models. Models will be available to investigators across the PS-ON. The Core will build on an already established PDX repository infrastructure that currently maintains sixty-two models covering ten different tumor histologies, with 2-3 new models are created each week. Early passage cell lines are created in parallel from these in vivo PDX models and they will also be available to the CR-PSOC investigators, as well as potentially to investigators in the PS-ON. These early passage cell lines will be utilized for in vitro experiments by all three CR-PSOC research projects. The phenotypic and genotypic uniformity of these cells will enable integration of data that across the three projects. The PDX Core will provide tissue and cell lines, where available, from existing breast cancer and glioma PDX to Project 1 investigators for in vivo characterization of subcellular metallome imbalances as potential quantitative markers of tumorigenicity. In addition, the Core will create new PDX models of human multiple myeloma and medulloblastoma since potassium imbalances have been implicated in the tumorigenicity and progression of these tumor types. PDX models will also be used by Project 1 investigators for imaging studies and to evaluate the therapeutic potential of targeting K+ channels support the imaging studies. The Core will develop acute myeloid leukemia (AML) and bladder cancer PDX models and cells for use by Project 2 to study the relationship between enhancer dysfunction and cancer. The Core will provide Project 3 investigators with cell lines derived from various PDX to enable determination of the relationship of variation of the distribution of condensin, cohesin, and SMC5/6 in chromosomes during interphase and mitosis with variations in chromosome mechanics across human tumor cell types.