Abstract
Amyloid precursor-like protein 2 (APLP2) is aberrantly expressed in pancreatic cancer. Here we showed that APLP2 is increased in pancreatic cancer metastases, particularly in metastatic lesions found in the diaphragm and intestine. Examination of matched human primary tumor-liver metastasis pairs showed that 38.1% of the patients had positive APLP2 expression in both the primary tumor and the corresponding liver metastasis. Stable knock-down of APLP2 expression (with inducible shRNA) in pancreatic cancer cells reduced the ability of these cells to migrate and invade. Loss of APLP2 decreased cortical actin and increased intracellular actin filaments in pancreatic cancer cells. Down-regulation of APLP2 decreased the weight and metastasis of orthotopically transplanted pancreatic tumors in nude mice.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / metabolism*
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Amyloid beta-Protein Precursor / genetics
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Amyloid beta-Protein Precursor / metabolism*
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Animals
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Anti-Bacterial Agents / pharmacology
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation*
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Down-Regulation / drug effects
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Doxycycline / pharmacology
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Female
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Flow Cytometry
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Humans
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Immunoblotting
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Immunohistochemistry
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Liver Neoplasms / metabolism
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Liver Neoplasms / secondary
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Lung Neoplasms / metabolism
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Lung Neoplasms / secondary
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Mice, Nude
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / metabolism*
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Pancreatic Neoplasms / pathology
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RNA Interference
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Tumor Burden / drug effects
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Tumor Burden / genetics
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Xenograft Model Antitumor Assays
Substances
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APLP2 protein, human
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Amyloid beta-Protein Precursor
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Anti-Bacterial Agents
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Nerve Tissue Proteins
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Doxycycline