Recoverin as a cancer-retina antigen
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In photoreceptor cells the Ca2+-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.
KeywordsParaneoplastic syndromes Paraneoplastic antigens Antibody T cell Tumor antigen
Cytotoxic T cell(s)
Paraneoplastic neurological syndrome(s)
Small cell lung cancer
This work was supported in parts by grants from the Cancer Research Institute/Elaine R. Shepard Memorial Investigator Award to S.B.E., the Ludwig Institute for Cancer Research and the Russian Foundation for Basic Research NN 04-04-48438 to P.P.Ph.
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