Relevance of amyloid precursor-like protein 2 C-terminal fragments in pancreatic cancer cells

  • Authors:
    • Haley L. Peters
    • Amit Tuli
    • Xiaojian Wang
    • Cuiling Liu
    • Zenggang Pan
    • Michel M. Ouellette
    • Michael A. Hollingsworth
    • Richard G. MacDonald
    • Joyce C. Solheim
  • View Affiliations

  • Published online on: July 13, 2012     https://doi.org/10.3892/ijo.2012.1553
  • Pages: 1464-1474
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Abstract

In some cellular systems, particularly neurons, amyloid precursor-like protein 2 (APLP2), and its highly homologous family member amyloid precursor protein (APP), have been linked to cellular growth. APLP2 and APP undergo regulated intramembrane proteolysis to produce C-terminal fragments. In this study, we found comprehensive expression of APLP2 C-terminal fragments in a panel of pancreatic cancer cell lines; however, APP C-terminal fragments were notably limited to the BxPC3 cell line. Extensive glycosaminoglycan modification on APLP2 was also found in the majority of pancreatic cancer cell lines. Glycosaminoglycan-modified and -unmodified APLP2, and particularly APLP2 C-terminal fragments, also demonstrated increased expression in oncogene-transformed pancreatic ductal cells. Additionally, elevated APLP2 levels were confirmed in human pancreatic cancer tissue. Downregulation of APLP2 and APP expression, alone or in combination, caused a decrease in the growth of a pancreatic cancer cell line with representatively low APP C-terminal fragment expression, the S2-013 cell line. Furthermore, we found that treatment with β-secretase inhibitors to block formation of APLP2 C-terminal fragments decreased the growth and viability of S2-013 cells, without affecting the survival of a non-transformed pancreatic ductal cell line. In conclusion, our studies demonstrate that abundant APLP2, but not APP, C-terminal fragment expression is conserved in pancreatic cancer cell lines; however, APP and APLP2 equally regulated the growth of S2-013 pancreatic cancer cells. Chiefly, our discoveries establish a role for APLP2 in the growth of pancreatic cancer cells and show that inhibitors preventing APLP2 cleavage reduce the viability of pancreatic cancer cells.
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October 2012
Volume 41 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Peters HL, Tuli A, Wang X, Liu C, Pan Z, Ouellette MM, Hollingsworth MA, MacDonald RG and Solheim JC: Relevance of amyloid precursor-like protein 2 C-terminal fragments in pancreatic cancer cells. Int J Oncol 41: 1464-1474, 2012
APA
Peters, H.L., Tuli, A., Wang, X., Liu, C., Pan, Z., Ouellette, M.M. ... Solheim, J.C. (2012). Relevance of amyloid precursor-like protein 2 C-terminal fragments in pancreatic cancer cells. International Journal of Oncology, 41, 1464-1474. https://doi.org/10.3892/ijo.2012.1553
MLA
Peters, H. L., Tuli, A., Wang, X., Liu, C., Pan, Z., Ouellette, M. M., Hollingsworth, M. A., MacDonald, R. G., Solheim, J. C."Relevance of amyloid precursor-like protein 2 C-terminal fragments in pancreatic cancer cells". International Journal of Oncology 41.4 (2012): 1464-1474.
Chicago
Peters, H. L., Tuli, A., Wang, X., Liu, C., Pan, Z., Ouellette, M. M., Hollingsworth, M. A., MacDonald, R. G., Solheim, J. C."Relevance of amyloid precursor-like protein 2 C-terminal fragments in pancreatic cancer cells". International Journal of Oncology 41, no. 4 (2012): 1464-1474. https://doi.org/10.3892/ijo.2012.1553