Prognostic Significance of Annexin A1 Expression in Pancreatic Ductal Adenocarcinoma

Chen, Congying; Shen, Jiaqing; Wang, Rui; Wan, Rong; Wang, Xingpeng

doi:10.7314/apjcp.2012.13.9.4707

Cited by 11 publications

(11 citation statements)

References 35 publications

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“…ANXA1 protein can perform numerous functions in cancer acting as either a tumour suppressor or an oncogene, depending on the cancer type 36 37 38 39 . In tissues from patients with PC, ANXA1 protein is over-expressed and has been correlated with poor differentiation and prognosis 5 6 although its role in the PC malignant transformation remains inadequately defined.…”

Section: Discussionmentioning

confidence: 99%

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Annexin A1 contributes to pancreatic cancer cell phenotype, behaviour and metastatic potential independently of Formyl Peptide Receptor pathway

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Forte

et al. 2016

Sci Rep

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Annexin A1 (ANXA1) is a Ca2+-binding protein over-expressed in pancreatic cancer (PC). We recently reported that extracellular ANXA1 mediates PC cell motility acting on Formyl Peptide Receptors (FPRs). Here, we describe other mechanisms by which intracellular ANXA1 could mediate PC progression. We obtained ANXA1 Knock-Out (KO) MIA PaCa-2 cells using the CRISPR/Cas9 genome editing technology. LC-MS/MS analysis showed altered expression of several proteins involved in cytoskeletal organization. As a result, ANXA1 KO MIA PaCa-2 partially lost their migratory and invasive capabilities with a mechanism that appeared independent of FPRs. The acquisition of a less aggressive phenotype has been further investigated in vivo. Wild type (WT), PGS (scrambled) and ANXA1 KO MIA PaCa-2 cells were engrafted orthotopically in SCID mice. No differences were found about PC primary mass, conversely liver metastatization appeared particularly reduced in ANXA1 KO MIA PaCa-2 engrafted mice. In summary, we show that intracellular ANXA1 is able to preserve the cytoskeleton integrity and to maintain a malignant phenotype in vitro. The protein has a relevant role in the metastatization process in vivo, as such it appears attractive and suitable as prognostic and therapeutic marker in PC progression.

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Section: Discussionmentioning

confidence: 99%

“…Numerous disturbances of biological pathways have been found in PC insurgence leading to tumour development and progression. Comparisons of protein profiles between PC and normal pancreas highlighted several proteomic alterations including the over-expression of annexin A1 (ANXA1) protein 4 5 6 .…”

mentioning

confidence: 99%

Annexin A1 contributes to pancreatic cancer cell phenotype, behaviour and metastatic potential independently of Formyl Peptide Receptor pathway

Belvedere

Bizzarro

Forte

et al. 2016

Sci Rep

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“…In PC there is an abnormally high expression of a number of important tyrosine kinase growth factors and receptors, like the Epidermal Growth Factor (EGF) family, which may contribute to the neoplasia growth by autocrine and paracrine effects [ 40 , 41 ]. Immunohistochemistry studies showed that EGF Receptor (EGFR) over-expression positively correlates with advanced tumour staging and lymph node metastasis [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Role of intracellular and extracellular annexin A1 in migration and invasion of human pancreatic carcinoma cells

et al. 2014

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BackgroundAnnexin A1 (ANXA1), a 37 kDa multifunctional protein, is over-expressed in tissues from patients of pancreatic carcinoma (PC) where the protein seems to be associated with malignant transformation and poor prognosis.MethodsThe expression and localization of ANXA1 in MIA PaCa-2, PANC-1, BxPC-3 and CAPAN-2 cells were detected by Western Blotting and Immunofluorescence assay. Expression and activation of Formyl Peptide Receptors (FPRs) were shown through flow cytometry/PCR and FURA assay, respectively. To investigate the role of ANXA1 in PC cell migration and invasion, we performed in vitro wound-healing and matrigel invasion assays.ResultsIn all the analyzed PC cell lines, a huge expression and a variable localization of ANXA1 in sub-cellular compartments were observed. We confirmed the less aggressive phenotype of BxPC-3 and CAPAN-2 compared with PANC-1 and MIA PaCa-2 cells, through the evaluation of Epithelial-Mesenchymal Transition (EMT) markers. Then, we tested MIA PaCa-2 and PANC-1 cell migration and invasiveness rate which was inhibited by specific ANXA1 siRNAs. Both the cell lines expressed FPR-1 and -2. Ac2-26, an ANXA1 mimetic peptide, induced intracellular calcium release, consistent with FPR activation, and significantly increased cell migration/invasion rate. Interestingly, in MIA PaCa-2 cells we found a cleaved form of ANXA1 (33 kDa) that localizes at cellular membranes and is secreted outside the cells, as confirmed by MS analysis. The importance of the secreted form of ANXA1 in cellular motility was confirmed by the administration of ANXA1 blocking antibody that inhibited migration and invasion rate in MIA PaCa-2 but not in PANC-1 cells that lack the 33 kDa ANXA1 form and show a lower degree of invasiveness. Finally, the treatment of PANC-1 cells with MIA PaCa-2 supernatants significantly increased the migration rate of these cells.ConclusionThis study provides new insights on the role of ANXA1 protein in PC progression. Our findings suggest that ANXA1 protein could regulate metastasis by favouring cell migration/invasion intracellularly, as cytoskeleton remodelling factor, and extracellularly like FPR ligand.

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“…In recent years, studies have revealed that partial molecules enjoy close relationships with cancer emergence and development, as well as drug resistance (Gerke et al, 2005;Chen et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Regulatory Mechanisms of Annexin-Induced Chemotherapy Resistance in Cisplatin Resistant Lung Adenocarcinoma

Wang

Xiao²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Adenocarcinoma of lung has high incidence and a poor prognosis, woith chemotherapy as the main therapeutic tool, most commonly with cisplatin. However, chemotherapy resistance develops in the majority of patients during clinic treatment. Mechanisms of resistance are complex and still unclear. Although annexin play important roles in various tumor resistance mechanisms, their actions in cisplatin-resistant lung adenocarcinoma remain unclear. Preliminary studies by our group found that in cisplatin-resistant lung cancer A549 cells and lung adenocarcinoma tissues, both mRNA and protein expression of annexins A1, A2 and A3 is increased. Using a library of annexin A1, A2 and A3 targeting combined molecules already established by ourselves we found that specific targeting decreased cisplatin-resistance. Taken together, the underlined effects of annexins A1, A2 and A3 on drug resistance and suggest molecular mechanisms in cisplatin-resistant A549 cells both in vivo and in vitro. Furthermore, the study points to improved research on occurrence and development of lung adenocarcinoma, with provision of effective targets and programmes for lung adenocarcinoma therapy in the clinic.

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Prognostic Significance of Annexin A1 Expression in Pancreatic Ductal Adenocarcinoma

Cited by 11 publications

References 35 publications

Annexin A1 contributes to pancreatic cancer cell phenotype, behaviour and metastatic potential independently of Formyl Peptide Receptor pathway

Annexin A1 contributes to pancreatic cancer cell phenotype, behaviour and metastatic potential independently of Formyl Peptide Receptor pathway

Role of intracellular and extracellular annexin A1 in migration and invasion of human pancreatic carcinoma cells

Regulatory Mechanisms of Annexin-Induced Chemotherapy Resistance in Cisplatin Resistant Lung Adenocarcinoma

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