Decreased prostate cancer cell migration by inhibition of the insulin-like growth factor II/Mannose-6-Phosphate receptor

The 270-kDa insulin-like growth factor II (IGF-II)/cation-independent mannose-6-phosphate receptor (MPR) is a multifunctional receptor protein. Endocytoses and intracellular transport of soluble enzymes bearing mannose6-phosphate (M-6-P) residues to lysosomes is mediated by the IGF-II/MPR. We examined human prostate cancer cells for IGF-II/MPR expression to determine whether this receptor mediates cell migration. PC3 human prostate cancer cells were studied for intracellular IGF-II/MPR by immunoblotting. PC3 cell surface IGF-II/MPR expression was assessed by flow cytometric analysis. Cell motility was quantitated by a scratch migration assay, and IGF-II/MPR blockade was achieved using M-6-P or affinity-purified rabbit anti-bovine cation-independent IGF-II/MPR immunoglobulin. IGF-II/MPR is expressed in the cytoplasm and on the surface of PC3 prostate cancer cells. The mean number of PC3 cells migrating per high powered field in medium containing polyclonal anti-IGF-II/MPR immunoglobulin or M-6-P decreased significantly (5 ± 4 cells and 34 ± 5 cells, respectively) compared with control medium containing mouse immunoglobulin G (70 ± 12 cells) or mannose-1-phosphate (67 ± 7 cells). This decreased PC3 cell migration following cell surface IGF-II/MPR blockade suggests that the IGF-II/MPR may play an important role in prostate cancer cell motility.