Recoverin as a cancer-retina antigen.
In photoreceptor cells the Ca(2+) -binding protein recoverin controls phosphorylation of the visual receptor rhodopsin by inhibiting rhodopsin kinase (GRK-1). It can also serve as a paraneoplastic antigen in the development of retinal degeneration in some patients with cancer. The aberrant expression of recoverin in cancer cells and the presence of autoantibodies against recoverin are essential for the occurrence of cancer-associated retinopathy, which finally results in the apoptosis of photoreceptor cells. Noteworthy in cancer patients, the aberrant recoverin expression and the appearance of autoantibodies against recoverin are more frequent than paraneoplastic syndromes. We suggest the term "cancer-retina antigens" for this kind of proteins like recoverin that are solely expressed in retina and tumor tissues and evoke antibodies and/or T cells in patients with cancer. The rare development of a paraneoplastic syndrome is possibly caused by this immune response and probably depends on further events allowing to overcome the blood-retina barrier and the immune privileged status of the retina. It is still unknown whether aberrantly expressed recoverin could have a specific function in cancer cells, though it is suggested that it can be functionally associated with G-protein-coupled receptor kinases. This paper reviews the present knowledge on paraneoplastic syndromes associated with the aberrant expression of recoverin. A possible application of recoverin as a potential target for immunotherapy of cancer is discussed.
Bazhin
Alexandr V
AV
Skin Cancer Unit (D070), German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Schadendorf
Dirk
D
Philippov
Pavel P
PP
Eichmüller
Stefan B
SB
D001323:Autoantibodies; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010257:Paraneoplastic Syndromes / Q000473:pathology; D051603:Recoverin; D012160:Retina / Q000166:cytology / Q000502:physiology*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology*
D001323:Autoantibodies; C496731:RCVRN protein, human; D051603:Recoverin; D051606:G-Protein-Coupled Receptor Kinase 1; C496764:GRK1 protein, human