Project description:Transcriptome profiling analysis was performed in 22 human prostate cancer organoids, 6 patient-derived xenografts (PDXs) and 7 cell lines.
Project description:Microarrays were used to assess differences between 1) human tumours that did and did not engraft, 2) human tumours and their matched primary xenografts, 3) early and late passage primary xenografts and 4) small and large primary xenografts for a series of esophageal patient and primary xenograft tumours
Project description:MCF10A series is one of the few human models of breast tumor progression. A derivative of MCF10A cells is the MCFDCIS, which reproducibly forms comedo DCIS-like lesions that spontaneously progress to invasive tumors. We used this model to explore the relative importance of myoepithelial cells and stromal fibroblasts in the in situ to invasive breast carcinoma transition. We use Affymetrix 11K XbaI or 250K StyI SNP arrays to analyze the MCF10A series cells and MCFDCIS derived xenografts for copy number changes and LOH (loss of heterozygosity). Keywords: Cell line, xenografts of time course/co-injection groups, different cell types isolated from xenografts
Project description:To understand if the generation of xenograft and organoid models of breast cancer alters DNA methylation, we compared the genome-wide methylation profile of matching patient tumors, patient derived xenografts, and organoid cultures derived from xenografts.
Project description:Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, we propagated a cohort of human breast tumors grown in the epithelium-free mammary fat pad of SCID/Beige and NOD/SCID/IL2γ-receptor null (NSG) mice, under a series of transplant conditions. Both models yielded stably transplantable xenografts at comparably high rates (~23% and ~19%, respectively). Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet. Overall, 32 stably transplantable xenograft lines were established, representing unique 25 patients. Most tumors yielding xenografts were “triple-negative” (ER-PR-HER2+) (n=19). However, we established lines from three ER-PR-HER2+ tumors, one ER+PR-HER2-, one ER+PR+HER2- and one “triple-positive” (ER+PR+HER2+) tumor. Serially passaged xenografts show biological consistency with the tumor of origin, are phenotypic stability across multiple transplant generations at the histological, transcriptomic, proteomic, and genomic levels, and show comparable treatment responses. Xenografts representing 12 patients, including two ER+ lines, showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource for preclinical studies investigating treatment response and metastasis.
Project description:Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, we propagated a cohort of human breast tumors grown in the epithelium-free mammary fat pad of SCID/Beige and NOD/SCID/IL2γ-receptor null (NSG) mice, under a series of transplant conditions. Both models yielded stably transplantable xenografts at comparably high rates (~23% and ~19%, respectively). Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet. Overall, 32 stably transplantable xenograft lines were established, representing unique 25 patients. Most tumors yielding xenografts were “triple-negative” (ER-PR-HER2+) (n=19). However, we established lines from three ER-PR-HER2+ tumors, one ER+PR-HER2-, one ER+PR+HER2- and one “triple-positive” (ER+PR+HER2+) tumor. Serially passaged xenografts show biological consistency with the tumor of origin, are phenotypic stability across multiple transplant generations at the histological, transcriptomic, proteomic, and genomic levels, and show comparable treatment responses. Xenografts representing 12 patients, including two ER+ lines, showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource for preclinical studies investigating treatment response and metastasis. The study was designed to determine how stable patient-derived xenografts are across multiple transplant generations in mice, and to determine how closely xenografts established with pre-treatment samples cluster with xenografts established with post-treatment samples. Overall, pre-treatment and post-treatment samples derived from the same patient cluster together, and multiple transplant generations of xenografts derived from an individual patient cluster together.