Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

A potential extracellular target for inositol phosphates and analogues with anticancer properties is identified. Proteins from detergent-solubilised HeLa cell lysates bound to a novel affinity column of myo-inositol 1,3,4,5,6-pentakisphosphate (InsP5) coupled to Affigel-10. One high-affinity ligand was fibrinogen Bβ. Inositol phosphates and analogues were able to elute purified fibrinogen from this matrix. InsP5 and the inositol phosphate mimic biphenyl 2,3',4,5',6-pentakisphosphate (BiPhP5) bind fibrinogen in vitro, and block the effects of fibrinogen in A549 cell-based assays of proliferation and migration. They are also able to prevent the fibrinogen-mediated activation of phosphatidylinositol 3-kinase. These effects of fibrinogen appear to be mediated through the intercellular adhesion molecule-1 (ICAM-1), as cells not expressing ICAM-1 fail to respond. In contrast, myo-inositol hexakisphosphate and the epimeric scyllo-inositol 1,2,3,4,5-pentakisphosphate were without effect. These findings are consistent with earlier reports that higher inositol phosphates have anticancer properties. This new mechanism of action and target for these extracellular inositol phosphates to have their effects allows a re-evaluation of earlier data.

Original publication

DOI

10.1166/msr.2012.1014

Type

Journal article

Journal

Messenger (Los Angel)

Publication Date

01/12/2012

Volume

1

Pages

160 - 166

Keywords

extracellular, fibrinogen, inositol phosphate, migration, proliferation