Limits...
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.

Show MeSH

Related in: MedlinePlus

Mice implanted with S2-013-APLP2-shRNA orthotopic pancreatic tumors and then given Dox had less extensive metastasesAfter euthanasia and dissection of the mice described in the legend for Figure 5, the percentages of tumor-bearing mice in the No Dox group or the Dox group that had metastases to various anatomic sites were recorded. The incidences of pancreatic tumor metastases were calculated as % incidence = number of mice with metastases in a particular site divided by total number of mice. Statistical significance was assessed by Fisher's Exact Test (Dox versus No Dox P-value for spleen 0.642, mesenteric lymph nodes 0.670, diaphragm 0.005, peritoneum 0.074, liver 0.189, kidney 0.008, intestine 0.017, and ovary 0.189).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4385836&req=5

Figure 7: Mice implanted with S2-013-APLP2-shRNA orthotopic pancreatic tumors and then given Dox had less extensive metastasesAfter euthanasia and dissection of the mice described in the legend for Figure 5, the percentages of tumor-bearing mice in the No Dox group or the Dox group that had metastases to various anatomic sites were recorded. The incidences of pancreatic tumor metastases were calculated as % incidence = number of mice with metastases in a particular site divided by total number of mice. Statistical significance was assessed by Fisher's Exact Test (Dox versus No Dox P-value for spleen 0.642, mesenteric lymph nodes 0.670, diaphragm 0.005, peritoneum 0.074, liver 0.189, kidney 0.008, intestine 0.017, and ovary 0.189).

Mentions: We also assessed the presence or absence of metastases in various anatomic sites within both groups of mice, and found that knockdown of APLP2 in the xenografted cancer cells caused major changes in the spread of the tumors. The percentages of mice with gross metastatic lesions in the diaphragm, intestine, and kidney were dramatically lower in the mice that had received Dox (Figure 7). In addition, the group of mice that received Dox to induce the APLP2 shRNA had a trend toward having significantly lower percentages with metastases involving the spleen, mesenteric lymph nodes, peritoneum, liver, and ovary, though the differences from No Dox controls at these additional sites were not significant at P<0.05 (Figure 7).


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)

Mice implanted with S2-013-APLP2-shRNA orthotopic pancreatic tumors and then given Dox had less extensive metastasesAfter euthanasia and dissection of the mice described in the legend for Figure 5, the percentages of tumor-bearing mice in the No Dox group or the Dox group that had metastases to various anatomic sites were recorded. The incidences of pancreatic tumor metastases were calculated as % incidence = number of mice with metastases in a particular site divided by total number of mice. Statistical significance was assessed by Fisher's Exact Test (Dox versus No Dox P-value for spleen 0.642, mesenteric lymph nodes 0.670, diaphragm 0.005, peritoneum 0.074, liver 0.189, kidney 0.008, intestine 0.017, and ovary 0.189).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385836&req=5

Figure 7: Mice implanted with S2-013-APLP2-shRNA orthotopic pancreatic tumors and then given Dox had less extensive metastasesAfter euthanasia and dissection of the mice described in the legend for Figure 5, the percentages of tumor-bearing mice in the No Dox group or the Dox group that had metastases to various anatomic sites were recorded. The incidences of pancreatic tumor metastases were calculated as % incidence = number of mice with metastases in a particular site divided by total number of mice. Statistical significance was assessed by Fisher's Exact Test (Dox versus No Dox P-value for spleen 0.642, mesenteric lymph nodes 0.670, diaphragm 0.005, peritoneum 0.074, liver 0.189, kidney 0.008, intestine 0.017, and ovary 0.189).
Mentions: We also assessed the presence or absence of metastases in various anatomic sites within both groups of mice, and found that knockdown of APLP2 in the xenografted cancer cells caused major changes in the spread of the tumors. The percentages of mice with gross metastatic lesions in the diaphragm, intestine, and kidney were dramatically lower in the mice that had received Dox (Figure 7). In addition, the group of mice that received Dox to induce the APLP2 shRNA had a trend toward having significantly lower percentages with metastases involving the spleen, mesenteric lymph nodes, peritoneum, liver, and ovary, though the differences from No Dox controls at these additional sites were not significant at P<0.05 (Figure 7).

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