Project description:Consensus Molecular Subtypes of colorectal cancer are recapitulated in in vitro and in vivo models [primary cell lines AMC/Palermo]
Project description:We have compared the gene expression profiles of primary colorectal cancers and colorectal liver metastases within the framework of the consensus molecular subtypes. This series represents a subset of the primary tumor samples.
Project description:Matrisome-focused integrative omics analysis reveals stromal phenotypes associated with consensus molecular subtypes in colorectal cancer
This reseaerch is conducted using colorectal cancer.
TMT 11plex experiment
Project description:We have analyzed transcriptomic intra-tumor heterogeneity among 2-4 multiregional samples from each of 98 primary colorectal cancers. We investigated the level and prognostic value of intra-tumor heterogeniety of the consensus molecular subtypes, and identified subtypes more robust to heterogeneity based on genes with uniform expression levels across tumor regions.
Project description:The study of breast cancer pathogenesis relies heavily on the use of established cell lines often derived from metastatic lesions, which while having significantly contributed to the knowledge of breast cancer biology may inadvertently limit the understanding of the mechanisms governing the metastatic process. Our goal was to establish primary cultures from dissociation of breast tumors in order to provide cellular models that may better recapitulate breast cancer pathogenesis and the metastatic process. These cellular models differ from recently developed patient derived xenograft models (PDX) in that they can be used for both in vitro and in vivo studies. Here we report the characterization of six cellular models derived from the dissociation of primary breast tumor specimens, referred to as “dissociated tumor (DT) cells”. Among the DT cells are those that are tumorigenic and metastatic in immunosuppressed mice, and a group of cancer-associated fibroblasts (CAFs). In vitro, DT cells were characterized by proliferation assays, colony formation assays, protein and gene expression profiling, including PAM50 predictor analysis. The latter showed DT cultures similar to their paired primary tumor and as belonging to the basal and Her2-enriched subtypes, offering novel cellular models of these ER-negative breast cancer subtypes. In vivo, three DT cultures are tumorigenic in NOD/SCID and NSG mice, and one of these is metastatic to lymph nodes and lung after orthotopic inoculation into the mammary fat pad, without excision of the primary tumor. DT cultures comprised of CAFs were isolated from luminal-A, Her2-enriched and basal primary tumors, providing subtype-specific components of the tumor microenvironment. Altogether, these DT cultures provide closer-to-primary cellular models for the study of breast cancer pathogenesis, metastasis and tumor microenvironment. reference x sample
