Project description:Prostate cancer discovery and translational research are hampered by a lack of preclinical models which accurately reproduce the biological heterogeneity observed in patients. Accordingly, we have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from primary prostate cancer tissue, and also new lines from metastatic tissue. Critically, the lines retained salient features of the original patient tumors, including histopathology, clinical marker expression, chromosomal aberration and gene expression profiles. Furthermore, they span major histopathological and molecular subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of complete neuroendocrine transdifferentiation. This publicly-available resource provides novel tools to advance mechanistic understanding of disease progression and response to therapy, and delivers clinically-relevant model systems for evaluation of preclinical drug efficacy. 3 primary tumors and 21 xenograft tumors
Project description:Prostate cancer discovery and translational research are hampered by a lack of preclinical models which accurately reproduce the biological heterogeneity observed in patients. Accordingly, we have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from primary prostate cancer tissue, and also new lines from metastatic tissue. Critically, the lines retained salient features of the original patient tumors, including histopathology, clinical marker expression, chromosomal aberration and gene expression profiles. Furthermore, they span major histopathological and molecular subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of complete neuroendocrine transdifferentiation. This publicly-available resource provides novel tools to advance mechanistic understanding of disease progression and response to therapy, and delivers clinically-relevant model systems for evaluation of preclinical drug efficacy. 3 primary tumors and 22 xenograft tumors
Project description:The inter-patient variability of tumor proteomes has been investigated on a large scale but many tumors display also intra-tumoral heterogeneity (ITH) regarding morphological and genetic features. To what extent the local proteome of tumors intrinsically differs remains largely unknown. Here, we used hepatocellular carcinoma (HCC) as a model system, to quantify both inter- and intra-tumor heterogeneity across human patient specimens with spatial resolution. We first defined proteomic features that robustly distinguish neoplastic from the directly adjacent non-neoplastic tissue by integrating proteomic data from human patient samples and genetically defined mouse models with available gene expression data. We then demonstrated the existence of intra-tumoral variations in protein abundance that re-occur across different patient samples, and affect clinically relevant proteins, even in the absence of obvious morphological differences or genetic alterations. Our work demonstrates the suitability and the benefits of using mass spectrometry based proteomics to analyze diagnostic tumor specimens with spatial resolution
Project description:Prostate cancer research is hampered by a lack of preclinical models which accurately reproduce clinical heterogeneity. We have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from prostate cancer biopsy tissue, and also new lines from metastatic tissue. The lines retained salient features of the original patient tumors, including histopathological and molecular characteristics. Furthermore, they span major subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of neuroendocrine transdifferentiation. This publicly-available resource provides novel tools for the next-generation of prostate cancer research and therapy development.
Project description:Prostate cancer research is hampered by a lack of preclinical models which accurately reproduce clinical heterogeneity. We have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from prostate cancer biopsy tissue, and also new lines from metastatic tissue. The lines retained salient features of the original patient tumors, including histopathological and molecular characteristics. Furthermore, they span major subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of neuroendocrine transdifferentiation. This publicly-available resource provides novel tools for the next-generation of prostate cancer research and therapy development.