Interferon-gamma reduces cell surface expression of annexin 2 and suppresses the invasive capacity of prostate cancer cells.

The effect of interferon-gamma (IFNgamma) treatment on cell surface protein expression was studied in the human prostate cancer cell line 1542CP3TX. IFNgamma 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, IFNgamma 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 IFNgamma 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. IFNgamma 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 IFNgamma-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 IFNgamma 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.