The Cell Biology Core provides major resources to the program project investigators, including normal human cells, an extensive library of characterized melanoma cell lines, patient-derived xenografts, and multiple models to study specific biological processes (Objective 1). The melanoma cell line library encompasses >400 cell lines, at least 200 with known genetic status. To exclude cross-contamination, all experimental cell lines are fingerprinted. Our normal cell panel includes: melanocytes, keratinocytes, fibroblasts, endothelial cells, and skin-derived stem cells. Other resources include adenoviral and lentiviral vectors for growth factors, adhesion molecules, and oncogenes and monoclonal antibodies to melanoma associated biomarkers Three-dimensional cultures of normal human skin (skin equivalents or organotypic cultures of skin) with a dermis of fibroblasts embedded in collagen and an epidermis of melanocytes/melanoma cells and keratinocytes, are also continuously available to the program investigators. This three-dimensional model is superior to standard cell culture techniques because it mimics the in vivo microenvironment for the melanocytes/melanoma cells. For screening studies the Core is providing a robotics-assisted spheroid culture model that allows investigations on melanoma cells displaying in vivo relevant architecture, cell-to cell contacts and invasion, in the presence of a collagen support matrix. The Core additionally provides subcutaneous melanoma growth models for standard experiments, including patient-derived xenografts that are exclusively maintained in vivo and using tissues provided by the Pathology Core B. For Objective 2, the Core will test compounds developed and selected for further analysis and has the knowledge and infrastructure for performing high-throughput screening both in two- and three-dimensional cultures. The responsibility of the Core is to test compounds in an expanded number of cell lines and in quality control testing through different biological assays. For Objective 3, the Core is available to train investigators of the Program in all biological assays and models. Overall, this Core will provide efficient and high quality service to all laboratories within this Program Project.

Public Health Relevance

This core supports the research projects with cell- and animal-based experimental tools and models, but also conducts experiments. The infrastructure encompasses libraries of human melanoma cell lines, viruses and antibodies, skin and tumor growth models, each reflecting different aspects of melanoma biology in patients. Most recent developments have added the capacity of the core to conduct high-throughput screening of compounds to identify novel inhibitors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA114046-06
Application #
8759652
Study Section
Special Emphasis Panel (ZCA1-RPRB-2 (M1))
Project Start
2013-09-25
Project End
2018-08-31
Budget Start
2013-09-25
Budget End
2014-08-31
Support Year
6
Fiscal Year
2013
Total Cost
$311,228
Indirect Cost
$99,578
Name
Wistar Institute
Department
Type
DUNS #
075524595
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Webster, Marie R; Xu, Mai; Kinzler, Kathryn A et al. (2015) Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells. Pigment Cell Melanoma Res 28:184-95
Leu, Julia I-Ju; Zhang, Pingfeng; Murphy, Maureen E et al. (2014) Structural basis for the inhibition of HSP70 and DnaK chaperones by small-molecule targeting of a C-terminal allosteric pocket. ACS Chem Biol 9:2508-16
Vultur, A; Villanueva, J; Krepler, C et al. (2014) MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines. Oncogene 33:1850-61
Streib, Manuel; Kraling, Katja; Richter, Kristin et al. (2014) An organometallic inhibitor for the human repair enzyme 7,8-dihydro-8-oxoguanosine triphosphatase. Angew Chem Int Ed Engl 53:305-9
Ma, Xiao-Hong; Piao, Sheng-Fu; Dey, Souvik et al. (2014) Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J Clin Invest 124:1406-17
Zhang, Pingfeng; Leu, Julia I-Ju; Murphy, Maureen E et al. (2014) Crystal structure of the stress-inducible human heat shock protein 70 substrate-binding domain in complex with peptide substrate. PLoS One 9:e103518
Wang, Tao; Ge, Yingbin; Xiao, Min et al. (2014) SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway. J Invest Dermatol 134:1108-18
Malecka, Kimberly A; Fera, Daniela; Schultz, David C et al. (2014) Identification and characterization of small molecule human papillomavirus E6 inhibitors. ACS Chem Biol 9:1603-12
Licciulli, Silvia; Maksimoska, Jasna; Zhou, Chun et al. (2013) FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. J Biol Chem 288:29105-14
Kastl, Anja; Dieckmann, Sandra; Wahler, Kathrin et al. (2013) Rhenium complexes with visible-light-induced anticancer activity. ChemMedChem 8:924-7

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