Project description:The present study describes a novel xenograft-based biomarker discovery platform and proves its usefulness in the discovery of novel serum markers for prostate cancer (PCa). By immunizing immuno-competent mice with serum from nude mice bearing PCa xenografts, an antibody response against xenograft-derived antigens was elicited. By probing protein microarrays with serum from immunized mice, several PCa-derived antigens were identified, of which a subset was successfully retrieved in serum from mice bearing PCa xenografts and validated in human serum samples of PCa patients. In conclusion, this novel method allows for the identification of low abundant cancer-derived serum proteins, circumventing dynamic range and host-response issues in standard patient cohort proteomics comparisons.
Project description:A set of 17 prostate cancer patient-derived xenografts (PDX, Lin et al 2014, Cancer research) was analyzed by mass spectrometry-based proteomics to characterize the effects of castration in vivo, and the proteome differences between NEPC and prostate adenocarcinomas.
Project description:We profiled the epigenomes of neuroendocrine prostate cancer and prostate adenocarcinoma patient-derived xenografts using ChIP-seq for transcription factors and histone modifications.
Project description:Developing animal models representating the cancer biology of advanced prostate cancer patients is challenging but essential for delivering individualized medical therapies. In an effort to develop patient derived xenograft (PDX) models, we took the metastatic site tissue from the rib lesion twice (ie, before and after enzalutamide treatment) over a twelve week period and implanted subcutaneously and under the renal capsule in immuno-deficient mice. To characterize and compare the genome and transcriptome landscapes of patient tumor tissues and the corresponding PDX models, we performed whole exome and transcriptome sequencing for metastatic tumor tissue as well as its derived PDXs. We demonstrated the feasibility of developping PDX models from patient who developed castrate-resistant prostate cancer. Our data suggested PDX models preserve the patient’s genomic and transcriptomic alterations in high fidelity, as illustrated by somatic mutation, copy number variation, gene fusion and gene expression. RNA sequencing of prostate cancer tumor tissue and derived xenograft using Illumina HiSeq 2000.
Project description:Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis.
Project description:Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis.
Project description:Raw mass spec files for the protein interactomes of MALAT1, polyadenylated RNA, and scrambled controls in mouse liver and patient derived prostate tumor xenografts XG147 and XG77 as determined by HyPR-MS.
Project description:Availability of patient-derived sarcoma models that closely mimic human tumors remains a significant gap in cancer research as these models may not recapitulate the spectrum of sarcoma heterogeneity seen in patients. To characterize patient-derived models for functional studies, we made proteomic comparisons with originating sarcomas representative of the three intrinsic subtypes by mass spectrometry. Human protein profiling was found to be retained with high fidelity in patient-derived models. Patient derived xenografts locally invade and colonize stroma in mice which enables unambiguous molecular discrimination of human proteins in the tumor from mouse proteins in the microenvironment. We characterized protein profiling of patient sarcoma tumors and mouse stroma by species-specific quantitative proteomics. We found that protein expression in mouse stroma was affected by the primary human tumor. Our results showed that levels of stromal proteins derived from the tumor were lowered in PDXs and cell lines and part of human stromal proteins were replaced by corresponding mouse proteins in PDXs. This suggests that the effects of the microenvironment on drug response may not reflect those in the primary tumor. This cross-species proteomic analysis in PDXs could potentially improve preclinical evaluation of treatment modalities and enhance the ability to predict clinical trial responses.
