Oncotarget

Research Papers:

Annexin 2A sustains glioblastoma cell dissemination and proliferation

Francesca Maule, Silvia Bresolin, Elena Rampazzo, Daniele Boso, Alessandro Della Puppa, Giovanni Esposito, Elena Porcù, Stefania Mitola, Giuseppe Lombardi, Benedetta Accordi, Manuela Tumino, Giuseppe Basso and Luca Persano _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:54632-54649. https://doi.org/10.18632/oncotarget.10565

Metrics: PDF 1780 views  |   HTML 2173 views  |   ?  


Abstract

Francesca Maule1, Silvia Bresolin1, Elena Rampazzo1,2, Daniele Boso1, Alessandro Della Puppa3, Giovanni Esposito4, Elena Porcù1, Stefania Mitola5, Giuseppe Lombardi6, Benedetta Accordi1, Manuela Tumino7, Giuseppe Basso1,7, Luca Persano1,2

1Department of Woman and Child Health, University of Padova, Padova, IT

2Istituto di Ricerca Pediatrica (IRP) – Città della Speranza, Padova, IT

3Neurosurgery Unit, University-Hospital of Padova, Padova, IT

4Istituto Oncologico Veneto, IRCCS, Padova, IT

5Experimental Oncology and Immunology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, IT

6Department of Clinical and Experimental Oncology, Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, IT

7Clinic of Pediatric Oncohematology, University-Hospital of Padova, Padova, IT

Correspondence to:

Luca Persano, email: luca.persano@unipd.it

Keywords: annexin 2A, glioblastoma, invasion, cell cycle, cytoskeletal remodeling

Received: March 09, 2016     Accepted: June 03, 2016     Published: July 13, 2016

ABSTRACT

Glioblastoma (GBM) is the most devastating tumor of the brain, characterized by an almost inevitable tendency to recur after intensive treatments and a fatal prognosis. Indeed, despite recent technical improvements in GBM surgery, the complete eradication of cancer cell disseminated outside the tumor mass still remains a crucial issue for glioma patients management. In this context, Annexin 2A (ANXA2) is a phospholipid-binding protein expressed in a variety of cell types, whose expression has been recently associated with cell dissemination and metastasis in many cancer types, thus making ANXA2 an attractive putative regulator of cell invasion also in GBM.

Here we show that ANXA2 is over-expressed in GBM and positively correlates with tumor aggressiveness and patient survival. In particular, we associate the expression of ANXA2 to a mesenchymal and metastatic phenotype of GBM tumors. Moreover, we functionally characterized the effects exerted by ANXA2 inhibition in primary GBM cultures, demonstrating its ability to sustain cell migration, matrix invasion, cytoskeletal remodeling and proliferation. Finally, we were able to generate an ANXA2-dependent gene signature with a significant prognostic potential in different cohorts of solid tumor patients, including GBM.

In conclusion, we demonstrate that ANXA2 acts at multiple levels in determining the disseminating and aggressive behaviour of GBM cells, thus proving its potential as a possible target and strong prognostic factor in the future management of GBM patients.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 10565