Role of α5β1 and αvβ3 integrins in relation to adhesion and spreading dynamics of prostate cancer cells interacting with fibronectin under in vitro conditions

Cell Biol Int. 2012 Oct 1;36(10):883-92.

Anna Stachurska a, Jerzy Elbanowski b, Hanna M. Kowalczyńska a*

a  Department of Biophysics, Medical Centre for Postgraduate Education, ul. Marymoncka 99, 01-813 Warsaw, Poland

b  Department of Informatics and Biomathematics , Medical Centre for Postgraduate Education, ul. Marymoncka 99, 01-813, Warsaw, Poland

 

BACKGROUND: The prostate cancer is among the most frequently detected malignant neoplasms in men. It is commonly accepted that integrin receptors may be regarded as a preclinical tumour marker, whereas their expression profile may play a key role in determining the degree of the invasiveness of cancer cells. Since cell dissemination and tumor metastases depend on the mechanism of interaction of cell integrins with proteins, we have studied the contribution of α5β1 and αvβ3 integrins of the prostate cancer PC-3 cells in in vitro interaction with fibronectin adsorbed on polystyrene surfaces. The response of cells to the signal derived from the adsorbed fibronectin was determined by qualitatively and semiquantitatively estimating cell adhesion, spreading and organization of cytoskeleton proteins, and also the participation of cell integrins in these processes.

MATERIAL AND METHODS: Interaction of human prostate cancer PC-3 cells (derived from bone metastases) with fibronectin adsorbed on sulfonated polystyrene surfaces of a defined chemical composition was studied. Density of fibronectin adsorbed on the polystyrene surface was equal to 500 ng/cm2. We measured cell adhesion, spreading dynamics and also cytoskeleton organization using antibodies against integrins (α5β1 and αvβ3) or a GRGDSP peptide. The dynamics of cell spreading was examined employing a phase contrast microscopy and automatic sequentional microscopic image registration with Lucia software. A computer-based analysis system and the Bitanal program were used for the imaging of cytoskeletal proteins in adhering cells.

RESULTS: Blocking the α5β1 receptor causes: (i) a decrease in the number of the adhered cells in the early phase of adhesion and (ii) a decrease in the dynamics of cell spreading and cell shape changes, and weaker reorganization of cytoskeletal proteins than in the control cells. Conversely, the blocking of the αvβ3 integrin: (i) causes no observable effect on the number of the adhered cells, however, (ii) causes an increase in the dynamics of cell spreading and cell shape changes, and stronger reorganization of cytoskeletal proteins than in the control cells. Integrin blocking carried out with a GRGDSP peptide causes a strong decrease in the number of the adhered cells, and a complete inhibition of the cell spreading.

Our results strongly suggest that the α5β1 integrin plays the main role in the adhesion and spreading of PC-3 cells interacting with fibronectin, whereas the αvβ3 integrinseems to regulate other receptors in the spreading process. Moreover, the obtained results confirm the key role of interaction between integrins and FNIII10 domain in the process of cell adhesion and spreading.

CONCLUSION: Albeit the roles of the α5β1 integrin and the αvβ3 one are different in the cell interaction with fibronectin, both these integrins are important in the process of prostate cancer metastases. The better understanding the mechanism of cell interaction via integrins may contribute to the development of effective anti-cancer therapy.

PMID: 22686483

 

Anna Stachurska-png1 Anna Stachurska-png2

 

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