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Amyloid precursor-like protein 2 (APLP2) affects the actin cytoskeleton and increases pancreatic cancer growth and metastasis.

Pandey P, Rachagani S, Das S, Seshacharyulu P, Sheinin Y, Naslavsky N, Pan Z, Smith BL, Peters HL, Radhakrishnan P, McKenna NR, Giridharan SS, Haridas D, Kaur S, Hollingsworth MA, MacDonald RG, Meza JL, Caplan S, Batra SK, Solheim JC - Oncotarget (2015)

Bottom Line: Here we showed that APLP2 is increased in pancreatic cancer metastases, particularly in metastatic lesions found in the diaphragm and intestine.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.

View Article: PubMed Central - PubMed

Affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.

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.

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Immunohistochemical analysis of APLP2 protein expression in human pancreatic tissues, primary pancreatic cancer tissues, and patient-matched metastatic lesions in the liver and lung(A) A comparison of the composite scores for APLP2 protein expression in normal, malignant primary, and metastatic tissues from pancreatic cancer patients. Statistical analysis was done using Student's t test with the Bonferroni correction. The graphing software for the scatter plot automatically indicates out-of-range values with different symbols (open circle or asterisks). (B) The left panel presents normal pancreas with a small duct (negative for APLP2 expression), and the right panel shows normal pancreas with weak APLP2 positivity in neuroendocrine cells. (C) In the left panel, APLP2 positive expression is shown in pancreatic cancer tissue, with cytoplasmic staining in the cancer cells. The right panel shows pancreatic cancer that is APLP2 negative and islet of Langerhans that is positive (indicated by an arrow). (D) Data are displayed showing the absence of detectable APLP2 in a pancreatic cancer section (left panel) and in normal colon tissue (right panel). (E) APLP2 negative staining in a section of liver metastatic tissue is shown. (F) APLP2 weak staining in liver metastatic tissue is demonstrated. (G) APLP2 moderate staining in liver metastatic tissue is presented. (H) APLP2 intense staining in liver metastatic tissue is shown. (I) APLP2 positivity in lung metastatic tissue is displayed. The scale bar represents 50 μm. Selected areas of focal staining are indicated by the arrows.
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Figure 2: Immunohistochemical analysis of APLP2 protein expression in human pancreatic tissues, primary pancreatic cancer tissues, and patient-matched metastatic lesions in the liver and lung(A) A comparison of the composite scores for APLP2 protein expression in normal, malignant primary, and metastatic tissues from pancreatic cancer patients. Statistical analysis was done using Student's t test with the Bonferroni correction. The graphing software for the scatter plot automatically indicates out-of-range values with different symbols (open circle or asterisks). (B) The left panel presents normal pancreas with a small duct (negative for APLP2 expression), and the right panel shows normal pancreas with weak APLP2 positivity in neuroendocrine cells. (C) In the left panel, APLP2 positive expression is shown in pancreatic cancer tissue, with cytoplasmic staining in the cancer cells. The right panel shows pancreatic cancer that is APLP2 negative and islet of Langerhans that is positive (indicated by an arrow). (D) Data are displayed showing the absence of detectable APLP2 in a pancreatic cancer section (left panel) and in normal colon tissue (right panel). (E) APLP2 negative staining in a section of liver metastatic tissue is shown. (F) APLP2 weak staining in liver metastatic tissue is demonstrated. (G) APLP2 moderate staining in liver metastatic tissue is presented. (H) APLP2 intense staining in liver metastatic tissue is shown. (I) APLP2 positivity in lung metastatic tissue is displayed. The scale bar represents 50 μm. Selected areas of focal staining are indicated by the arrows.

Mentions: APLP2 expression was also determined in a separate set of pancreatic cancer tissue array samples, which contained patient-matched primary and metastasis samples (Figure 2A). Among these primary pancreatic, liver and lung metastatic tumors, the frequencies of positive APLP2 expression were 66.66% (16/24), 52.17% (12/23), and 100% (1/1), respectively. We did not observe APLP2 expression in the ductal cells of any of the 5 normal pancreas samples in this set (Figure 2B). Some of the endocrine cells within normal pancreas specimens showed variable APLP2 immunoreactivity, demonstrating that APLP2 protein expression differs slightly among the cell types in the normal pancreas (Figure 2B). Figure 2C illustrates APLP2-positive (left panel) and APLP2-negative (right panel) sections of pancreatic cancer tissue (with the right panel including an islet of Langerhans that is APLP2-positive, indicated by the arrow).


Amyloid precursor-like protein 2 (APLP2) affects the actin cytoskeleton and increases pancreatic cancer growth and metastasis.

Pandey P, Rachagani S, Das S, Seshacharyulu P, Sheinin Y, Naslavsky N, Pan Z, Smith BL, Peters HL, Radhakrishnan P, McKenna NR, Giridharan SS, Haridas D, Kaur S, Hollingsworth MA, MacDonald RG, Meza JL, Caplan S, Batra SK, Solheim JC - Oncotarget (2015)

Immunohistochemical analysis of APLP2 protein expression in human pancreatic tissues, primary pancreatic cancer tissues, and patient-matched metastatic lesions in the liver and lung(A) A comparison of the composite scores for APLP2 protein expression in normal, malignant primary, and metastatic tissues from pancreatic cancer patients. Statistical analysis was done using Student's t test with the Bonferroni correction. The graphing software for the scatter plot automatically indicates out-of-range values with different symbols (open circle or asterisks). (B) The left panel presents normal pancreas with a small duct (negative for APLP2 expression), and the right panel shows normal pancreas with weak APLP2 positivity in neuroendocrine cells. (C) In the left panel, APLP2 positive expression is shown in pancreatic cancer tissue, with cytoplasmic staining in the cancer cells. The right panel shows pancreatic cancer that is APLP2 negative and islet of Langerhans that is positive (indicated by an arrow). (D) Data are displayed showing the absence of detectable APLP2 in a pancreatic cancer section (left panel) and in normal colon tissue (right panel). (E) APLP2 negative staining in a section of liver metastatic tissue is shown. (F) APLP2 weak staining in liver metastatic tissue is demonstrated. (G) APLP2 moderate staining in liver metastatic tissue is presented. (H) APLP2 intense staining in liver metastatic tissue is shown. (I) APLP2 positivity in lung metastatic tissue is displayed. The scale bar represents 50 μm. Selected areas of focal staining are indicated by the arrows.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 2: Immunohistochemical analysis of APLP2 protein expression in human pancreatic tissues, primary pancreatic cancer tissues, and patient-matched metastatic lesions in the liver and lung(A) A comparison of the composite scores for APLP2 protein expression in normal, malignant primary, and metastatic tissues from pancreatic cancer patients. Statistical analysis was done using Student's t test with the Bonferroni correction. The graphing software for the scatter plot automatically indicates out-of-range values with different symbols (open circle or asterisks). (B) The left panel presents normal pancreas with a small duct (negative for APLP2 expression), and the right panel shows normal pancreas with weak APLP2 positivity in neuroendocrine cells. (C) In the left panel, APLP2 positive expression is shown in pancreatic cancer tissue, with cytoplasmic staining in the cancer cells. The right panel shows pancreatic cancer that is APLP2 negative and islet of Langerhans that is positive (indicated by an arrow). (D) Data are displayed showing the absence of detectable APLP2 in a pancreatic cancer section (left panel) and in normal colon tissue (right panel). (E) APLP2 negative staining in a section of liver metastatic tissue is shown. (F) APLP2 weak staining in liver metastatic tissue is demonstrated. (G) APLP2 moderate staining in liver metastatic tissue is presented. (H) APLP2 intense staining in liver metastatic tissue is shown. (I) APLP2 positivity in lung metastatic tissue is displayed. The scale bar represents 50 μm. Selected areas of focal staining are indicated by the arrows.
Mentions: APLP2 expression was also determined in a separate set of pancreatic cancer tissue array samples, which contained patient-matched primary and metastasis samples (Figure 2A). Among these primary pancreatic, liver and lung metastatic tumors, the frequencies of positive APLP2 expression were 66.66% (16/24), 52.17% (12/23), and 100% (1/1), respectively. We did not observe APLP2 expression in the ductal cells of any of the 5 normal pancreas samples in this set (Figure 2B). Some of the endocrine cells within normal pancreas specimens showed variable APLP2 immunoreactivity, demonstrating that APLP2 protein expression differs slightly among the cell types in the normal pancreas (Figure 2B). Figure 2C illustrates APLP2-positive (left panel) and APLP2-negative (right panel) sections of pancreatic cancer tissue (with the right panel including an islet of Langerhans that is APLP2-positive, indicated by the arrow).

Bottom Line: Here we showed that APLP2 is increased in pancreatic cancer metastases, particularly in metastatic lesions found in the diaphragm and intestine.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.

View Article: PubMed Central - PubMed

Affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.

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.

Show MeSH
Related in: MedlinePlus