Dataset Information

Mouse EL4 Tumor Proteome Comparison via LC-MSMS

ABSTRACT: The EL4 mouse tumor model is widely utilized within the field of oncology due to its ease of use and excellent response to chemotherapy, with tumors typically experiencing a reduction in mass of 70% following chemotherapy treatment with cyclophosphamide and etoposide for three days. As not much is known regarding the biochemical changes that result in these drastic reductions in tumor mass, we decided to analyze treated and untreated tumors using shotgun proteomics to identify the changes that occur in relative protein abundance following chemotherapeutic treatment, which will help determine the biological processes resulting in tumor death.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): T Cell, Lymph Node

DISEASE(S): Lymphoma

SUBMITTER: David Kramer

LAB HEAD: Richard P Fahlman

PROVIDER: PXD005592 | Pride | 2017-05-19

REPOSITORIES: Pride

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Publications

Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase-6 during tumor cell death in vivo.

Kramer David A DA Eldeeb Mohamed A MA Wuest Melinda M Mercer John J Fahlman Richard P RP

Proteomics 20170601 12

The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in-depth quantitative pr ...[more]

PMID: 28508578

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Project description:Head and neck squamous cell carcinoma (HNSCC) is a deadly and disfiguring disease for which better systemic therapy is desperately needed. The development of new therapies for HNSCC and the understanding of its biology both depend upon clinically relevant animal models. An increasingly promising xenograft model, the patient derived xenograft (PDX), is developed by surgically implanting tumor tissue directly from a patient into an immunocompromised mouse. We transplanted 30 HNSCC primary tumors directly into mice. The histology and stromal components were analyzed using immunohistochemistry. Gene expression analysis with Affymetrix U133A-microarrays was conducted on patient tumors, including third generation and one tenth generation PDX; one PDX-derived cell line; and 2 established HNSCC cell lines. Five of 30 (17%) transplanted tumors could be serially passaged and used for therapeutic and mechanistic studies. One cell line has been established from a tongue primary. The tumors maintained the histologic appearance of the parent tumor although human stromal components were lost upon engraftment. One PDX model was derived from an HPV-positive tumor. From the >54,000 probes tested, there were widespread differences in gene expression between the tumors growing in mice vs. the corresponding human tumors from which they were derived. For genes differing between parent tumors and human cell lines in culture, the PDXs’ expression pattern was very similar to that of the parent tumors. There were also widespread expression differences between the human tumors that subsequently grew in mice vs. those that did not - suggesting that this model enriches for cancers with distinct biological features. Our results demonstrate the feasibility of a PDX model of HNSCC. Gene expression patterns suggest that the PDX more closely recapitulated the parental tumor than do cells in culture. The histology of the tumors in mice is similar to that of the same tumor in humans. Additionally, gene expression patterns and histology are stable over multiple generations. We transplanted HNSCC primary tumors directly into mice. Gene expression analysis with Affymetrix U133A-microarrays was conducted on patient tumors, including third generation and one tenth generation PDX; one PDX-derived cell line; and 2 established HNSCC cell lines.

Dataset Information

Mouse EL4 Tumor Proteome Comparison via LC-MSMS

Publications

Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase-6 during tumor cell death in vivo.

Similar Datasets

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