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Amyloid Precursor-like Protein 2 Expression Increases during Pancreatic Cancer Development and Shortens the Survival of a Spontaneous Mouse Model of Pancreatic Cancer. Cancers (Basel) 2021 Mar 26;13(7)

Date

04/04/2021

Pubmed ID

33810510

Pubmed Central ID

PMC8036577

DOI

10.3390/cancers13071535

Scopus ID

2-s2.0-85102991803

Abstract

In the United States, pancreatic cancer is a major cause of cancer-related deaths. Although substantial efforts have been made to understand pancreatic cancer biology and improve therapeutic efficacy, patients still face a bleak chance of survival. A greater understanding of pancreatic cancer development and the identification of novel treatment targets are desperately needed. Our analysis of gene expression data from patient samples showed an increase in amyloid precursor-like protein 2 (APLP2) expression within primary tumor epithelium relative to pancreatic intraepithelial neoplasia (PanIN) epithelial cells. Augmented expression of APLP2 in primary tumors compared to adjacent stroma was also observed. Genetically engineered mouse models of spontaneous pancreatic ductal adenocarcinoma were used to investigate APLP2's role in cancer development. We found that APLP2 expression intensifies significantly during pancreatic cancer initiation and progression in the LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mouse model, as shown by immunohistochemistry analysis. In studies utilizing pancreas-specific heterozygous and homozygous knockout of APLP2 in the KPC mouse model background, we observed significantly prolonged survival and reduced metastatic progression of pancreatic cancer. These results demonstrate the importance of APLP2 in pancreatic cancer initiation and metastasis and indicate that APLP2 should be considered a potential therapeutic target for this disease.

Author List

Poelaert BJ, Knoche SM, Larson AC, Pandey P, Seshacharyulu P, Khan N, Maurer HC, Olive KP, Sheinin Y, Ahmad R, Singh AB, Batra SK, Rachagani S, Solheim JC

Author

Yuri M. Sheinin MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin