Investigating the role of ADAM10 in pancreatic tumor differentiation

Peverley, L. V., Halbrook, C. J., Hall, J. C., Ardito, C. M., Crawford, H. C. (July 2015) Investigating the role of ADAM10 in pancreatic tumor differentiation. Cancer Research, 75 (Supple). A77. ISSN 0008-5472

DOI: 10.1158/1538-7445.panca2014-a77


Pancreatic adenocarcinoma (PDAC) is the 4th most common cause of cancer related deaths in the United States and has a dismal 5-year survival rate of 6%. This prognosis is attributed the disease’s fast and asymptomatic progression to metastasis, leading to late diagnosis upon which time there are few treatment options available. The A Disintegrin and Metalloproteinase (ADAM) family are sheddase proteins known to regulate cell adhesion and function. This regulation can allow ADAMs to influence the ability of tumor cells to disseminate from the primary tumor and metastasize to distant organs. ADAM10, which is seen to be up-regulated in both chronic pancreatitis and PDAC, cleaves a variety of substrates including several cell adhesion molecules such as L1-CAM, N-Cadherin, and E-Cadherin. Using a conditional knockout for ADAM10 in the Kras+/G12D;Ptf1a+/Cre (KC) mouse model of pancreatic cancer, we have observed an absence of metastasis when ADAM10 is genetically ablated. To investigate the potential role that ADAM10 plays in this, we used a shRNA approach to knock-down ADAM10 expression in various human pancreatic cancer cells lines. Analysis of these cell lines suggests a partial restoration of a less aggressive, differentiated phenotype, consistent with the increased longevity of the ADAM10 knockout KC mice.

Item Type: Paper
Additional Information: Meeting Abstract
Subjects: diseases & disorders > cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > differentiation
Publication Type > Meeting Abstract
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > metalloproteinases
diseases & disorders > cancer > metastasis
diseases & disorders > cancer > cancer types > pancreatic cancer
CSHL Authors:
Communities: CSHL labs > Tuveson lab
Depositing User: Matt Covey
Date: 1 July 2015
Date Deposited: 25 Mar 2016 19:33
Last Modified: 06 Feb 2018 15:14

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