Expression of the onconeural protein CDR1 in cerebellum and ovarian cancer

Abstract

Cerebellar degeneration related protein 1 (CDR1) is expressed in the cerebellum, and CDR1 antibodies have been associated with paraneoplastic cerebellar degeneration (PCD). In this study, we examined CDR1 expression in cerebellum and in ovarian and breast tumors, as well as the intracellular localization of CDR1 in cancer cells in culture. CDR1 was strongly expressed in the cytosol and dendrites of Purkinje cells and in interneurons of the molecular layer in cerebellum. CDR1 was also present in ovarian and breast tumors, as well as in ovarian and breast cancer cell lines, but was not present in normal breast or ovarian tissue. In cells overexpressing CDR1, CDR1 localized close to the plasma membrane in a polarized pattern at one edge. CDR1 was strongly expressed on the outer surface, apparently in filopodias or lamellipodias, in cells endogenously expressing CDR1. Overexpression of CDR1 showed a 37 and a 45 kDa band in western blot. The 37-kDa isoform was present in 16 ovarian cancer lysates, while the 45-kDa isoform was only found in three ovarian cancer patients. The presence of CDR1 in ovarian cancer was not associated with PCD. CDR1 antibodies were only found in serum from one patient with PCD and ovarian tumor with metastases. Therefore, CDR1 is probably not a marker for PCD. However, CDR1 may be associated with cell migration and differentiation.