Clinicopathological Roles of Aberrantly Expressed Recoverin in Malignant Tumor Cells

Abstract

Purpose: Cancer-associated retinopathy (CAR) is an ocular manifestation of a paraneoplastic syndrome whereby immunological reactions toward recoverin, a retina-specific calcium binding protein, and other retinal antigens aberrantly expressed in tumor cells are elicited. As a consequence, photoreceptor cell degeneration is induced. To elucidate the pathological role of the aberrantly expressed recoverin, we studied the recoverin expression levels in various malignant tumors and the effects of the expressed recoverin on the sensitivity to anti-cancer drugs. Methods: Recoverin expression levels were determined by immunohistochemistry with anti-human recoverin monoclonal antibody on multiple tissue arrays obtained from several lung, stomach, colon and other cancers. In the presence of several anti-cancer drugs, including anti-tumor antibiotics, plant alkaloids and anti-metabolites, cytotoxicity assay was performed using recoverin-positive or recoverin-negative A549 cells originating from human lung adenocarcinoma. Results: Immunofluorescence labeling revealed that recoverin immunoreactivities were detected at approximately 10–40% of malignant tumor tissues. Cytotoxic effects by anti-cancer drugs were higher in recoverin-positive A549 cells as compared to recoverin-negative cells. Conclusion: The present data may correlate with the previous observation that recoverin-expressing cancer cells induced tumor immunity and a favorable prognosis for primary cancer in CAR patients.