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J. Biol. Chem., Vol. 283, Issue 18, 12595-12603, May 2, 2008

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Interferon- Reduces Cell Surface Expression of Annexin 2 and Suppresses the Invasive Capacity of Prostate Cancer Cells^*

Claire Hastie, John R. Masters, Stephen E. Moss^¶, and Soren Naaby-Hansen^||1

From the School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth, Hampshire PO1 2UP, United Kingdom, Prostate Cancer Research Centre, Royal Free and University College London Medical School, London W1W 7EJ, United Kingdom, ^¶Division of Cell Biology, Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom, and the ^||Department of Clinical Immunology, Aalborg Sygehus, Århus University Hospital, DK-9100 Aalborg, Denmark

The effect of interferon- (IFN) treatment on cell surface protein expression was studied in the human prostate cancer cell line 1542CP3TX. IFN increased both the number and abundance of proteins in membrane fractions. In contrast, the expression of annexin 2 and its binding partner p11 decreased by 4-fold after 24 h of exposure, with the remaining anx2_t complexes localized to lipid rafts. Within the same time scale, IFN reduced the abundance of the peripherally attached, anx2_t-associated proteases procathepsin B and plasminogen. The invasive capacity of the cancer cells was reduced by treatment with IFN or antibody to annexin 2 in 1542CP3TX cells, but not in LNCaP, an annexin 2-negative prostate cancer cell line. Expression of annexin 2 in LNCaP cells increased their invasiveness. IFN induced calpain expression and activation and increased the phosphorylation and degradation of the calpain substrate ABCA1 in 1542CP3TX cancer cells. Surface expression of annexin 2 was reduced in cells treated with glyburide, an ABCA1 inhibitor, whereas inhibition of calpain abrogated IFN-induced annexin 2 down-regulation and suppression of Matrigel invasion. The findings suggest annexin 2 externalization is coupled to lipid efflux in prostate epithelium and that IFN induces down-regulation of the protease-binding anx2_t scaffold at the cell surface and consequently acts to suppress invasiveness through calpain-mediated degradation of the lipid transporter ABCA1.

Received for publication, January 9, 2008 , and in revised form, January 18, 2008.

^* This work was supported by the Ludwig Institute for Cancer Research, UCL Branch, London, and by National Cancer Research Institute Grant G0100116 and National Institutes of Health Grant RO1 AG14960. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1-5.

¹ To whom correspondence should be addressed: Klinisk Immunologisk Afdeling, Aalborg Sygehus Nord, 9100 Aalborg, Denmark. E-mail: sonh{at}rn.dk.

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				A. L. Harzstark and E. J. Small Immunotherapeutics in Development for Prostate Cancer Oncologist, April 1, 2009; 14(4): 391 - 398. [Abstract] [Full Text] [PDF]