2015
DOI: 10.1126/scisignal.aaa5823
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Semaphorin 3D autocrine signaling mediates the metastatic role of annexin A2 in pancreatic cancer

Abstract: Most patients with pancreatic ductal adenocarcinoma (PDA) present with metastatic disease at the time of diagnosis or will recur with metastases after surgical treatment. Semaphorin–plexin signaling mediates the migration of neuronal axons during development and of blood vessels during angiogenesis. The expression of the gene encoding semaphorin 3D (Sema3D) is increased in PDA tumors, and the presence of antibodies against the pleiotropic protein annexin A2 (AnxA2) in the sera of some patients after surgical r… Show more

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Cited by 95 publications
(105 citation statements)
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“…This model recapitulates PDAC tumour progression but is in a mixed 129/SvJae/C57BL/6 background. Therefore, the original KPC mouse was backcrossed into a C57BL/6 background for nine generations and pancreatic tumours from these mice were harvested to produce primary epithelial KPC lines, which were kindly provided by Dr Elizabeth Jaffee for use in these studies 19. Cells were maintained in RPMI 1640 supplemented with 10% heat‐inactivated fetal bovine serum, 1% minimum essential medium non‐essential amino acids, 1 mM sodium pyruvate, and 50 U/mL penicillin/streptomycin (Gibco, Gaithersburg, MD, USA), with incubators maintained at 37°C and 5% CO 2 .…”
Section: Methodsmentioning
confidence: 99%
“…This model recapitulates PDAC tumour progression but is in a mixed 129/SvJae/C57BL/6 background. Therefore, the original KPC mouse was backcrossed into a C57BL/6 background for nine generations and pancreatic tumours from these mice were harvested to produce primary epithelial KPC lines, which were kindly provided by Dr Elizabeth Jaffee for use in these studies 19. Cells were maintained in RPMI 1640 supplemented with 10% heat‐inactivated fetal bovine serum, 1% minimum essential medium non‐essential amino acids, 1 mM sodium pyruvate, and 50 U/mL penicillin/streptomycin (Gibco, Gaithersburg, MD, USA), with incubators maintained at 37°C and 5% CO 2 .…”
Section: Methodsmentioning
confidence: 99%
“…In addition, they found that semaphorin 3D (Sema3D) is responsible for directing axonal extension during neuron growth and development. ANXA2 promotes the secretion of Sema3D by PDAC cells, which may promote the infiltration of PDAC cells through neural invasion [15].…”
Section: Discussionmentioning
confidence: 99%
“…However, several possibly clinically relevant observations with this strain have been made in recent years (Table 3). Crossing a sophisticated mouse model for the development of pancreatic ductal adenocarcinoma (PDA) with the AnxA2 -/-strain revealed a prominent role for AnxA2 in metastatic events driven by pancreatic cancers (Foley et al, 2015). While primary pancreatic tumors from AnxA2-deficient animals and controls were comparable, the metastatic potential of the PDA tumors from AnxA2 KO animals was substantially reduced.…”
Section: Anxa2 Ko Micementioning
confidence: 99%
“…This may be relevant for pulmonary function, but may extend to other disorders associated with COL6 deficiency (Dassah et al, 2014). In addition, this could also be related to migratory and invasive properties of pancreatic cancer cells (Foley et al, 2015) (Table 3). A few studies in the AnxA2 KO strain have now also provided initial evidence that AnxA2 contributes to membrane organization and transport along endocytic routes.…”
Section: Anxa2 Ko Micementioning
confidence: 99%
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