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Article

Amyloid Precursor-like Protein 2 Expression Increases during Pancreatic Cancer Development and Shortens the Survival of a Spontaneous Mouse Model of Pancreatic Cancer

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Eppley Institute for Research in Cancer & Allied Diseases and the Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA
2
Department of Biochemistry & Molecular Biology and the Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA
3
Columbia University Department of Medicine and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA
4
Department of Pathology and Microbiology and the Fred & Pamela Buffett Cancer Center, Omaha, NE 68198, USA
*
Author to whom correspondence should be addressed.
Current address: Georgiamune, Gaithersburg, MD 20878, USA.
Current address: Department of Laboratory Medicine, Karolinska University Hospital Huddinge, SE-14157 Stockholm, Sweden.
§
Current address: Klinikum rechts der Isar, II. Medizinische Klinik, Technische Universität München, 81675 Munich, Germany.
Current address: Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Academic Editors: Sumit Sahni, Anubhav Mittal and Jaswinder Samra
Cancers 2021, 13(7), 1535; https://doi.org/10.3390/cancers13071535
Received: 28 February 2021 / Revised: 17 March 2021 / Accepted: 21 March 2021 / Published: 26 March 2021
(This article belongs to the Special Issue Recent Advances in Pancreatic Ductal Adenocarcinoma)
As pancreatic cancer is a disease with a high fatality rate, a better understanding of how it develops and the identification of new potential targets for its treatment are greatly needed. In this current study, we showed that the expression of amyloid precursor-like protein 2 (APLP2) in pancreatic cancer epithelial cells is higher than in precursor lesion epithelial cells, thus indicating that APLP2 increases during human pancreatic cancer development. We also generated a new mouse model that demonstrated the deletion of APLP2 expression specifically within the pancreas prolongs survival and decreases metastasis for mice with pancreatic cancer. Taken together, these findings open a new avenue toward comprehending and treating pancreatic cancer.
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. View Full-Text
Keywords: amyloid precursor-like protein 2; mouse model; pancreatic cancer amyloid precursor-like protein 2; mouse model; pancreatic cancer
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MDPI and ACS Style

Poelaert, B.J.; Knoche, S.M.; Larson, A.C.; Pandey, P.; Seshacharyulu, P.; Khan, N.; Maurer, H.C.; Olive, K.P.; Sheinin, Y.; Ahmad, R.; Singh, A.B.; Batra, S.K.; Rachagani, S.; Solheim, J.C. Amyloid Precursor-like Protein 2 Expression Increases during Pancreatic Cancer Development and Shortens the Survival of a Spontaneous Mouse Model of Pancreatic Cancer. Cancers 2021, 13, 1535. https://doi.org/10.3390/cancers13071535

AMA Style

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. Amyloid Precursor-like Protein 2 Expression Increases during Pancreatic Cancer Development and Shortens the Survival of a Spontaneous Mouse Model of Pancreatic Cancer. Cancers. 2021; 13(7):1535. https://doi.org/10.3390/cancers13071535

Chicago/Turabian Style

Poelaert, Brittany J., Shelby M. Knoche, Alaina C. Larson, Poomy Pandey, Parthasarathy Seshacharyulu, Nuzhat Khan, H. C. Maurer, Kenneth P. Olive, Yuri Sheinin, Rizwan Ahmad, Amar B. Singh, Surinder K. Batra, Satyanarayana Rachagani, and Joyce C. Solheim. 2021. "Amyloid Precursor-like Protein 2 Expression Increases during Pancreatic Cancer Development and Shortens the Survival of a Spontaneous Mouse Model of Pancreatic Cancer" Cancers 13, no. 7: 1535. https://doi.org/10.3390/cancers13071535

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