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- W2022023715 abstract "Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCPancreatic ductal adenocarcinoma (PDA) is the 4th leading cause of cancer related death in the U.S. This disease has a poor prognosis due to late detection and rapid progression to metastasis. ADAM10 is a membrane bound metalloproteinase responsible for shedding bioactive molecules and inducing regulated intra-membrane proteolysis of cell surface proteins such as Notch. Both ADAM10 and Notch are highly expressed in patients with PDA, with the latter being implicated in PDA progression. We have found that genetic ablation of ADAM10 in the KrasG12D/+;Ptf1aCre/+ mouse PDA model altered tumor character to favor a cystic phenotype, mixed with low grade pancreatic intraepithelial neoplasia (PanIN) and PDA. Though ADAM10 knockout mice retain the ability to form locally invasive cancer, they live 50% longer than control mice, essentially to a full 2-year life span. The phenotypes we observe closely mimic Notch-2 knockout mice, consistent with ADAM10’s role as the primary Notch activating proteinase. Further examination revealed that ADAM10 knockout mice did not show significant liver metastasis compared to control, despite their local invasiveness. The mechanism through which ADAM 10 controls a cancer cell's ability to establish distant metastases will be explored.Citation Format: Jason C. Hall, Howard C. Crawford. Ablation of a disintegrin and metalloproteinase 10 (ADAM 10) induces significant pancreatic tumor heterogeneity and blocks cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5015. doi:10.1158/1538-7445.AM2013-5015" @default.
- W2022023715 created "2016-06-24" @default.
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- W2022023715 date "2013-04-15" @default.
- W2022023715 modified "2023-09-25" @default.
- W2022023715 title "Abstract 5015: Ablation of a disintegrin and metalloproteinase 10 (ADAM 10) induces significant pancreatic tumor heterogeneity and blocks cancer metastasis." @default.
- W2022023715 doi "https://doi.org/10.1158/1538-7445.am2013-5015" @default.
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