Trophoblast glycoprotein is a novel therapeutic target for extramammary Paget disease

Abstract Extramammary Paget disease (EMPD) is a rare skin cancer mainly found in the anogenital area of older people. It remains challenging to treat advanced EMPD due to the lack of effective treatments. The development of novel therapeutic approaches is thus strongly desired, but EMPD’s rarity and the lack of an appropriate in vitro model have impeded investigation of this disease. The aim of this work is to evaluate trophoblast glycoprotein (TPBG) as a promising therapeutic target for EMPD. To achieve this, TPBG expression was first analyzed in 124 (116 primary and 8 metastatic) samples from 116 EMPD patients. Using a recently established patient-derived EMPD cell line, KS-EMPD-1, the function of TPBG was assessed in vitro. TPBG was expressed in patients’ EMPD lesions with various staining intensities. It was also expressed in KS-EMPD-1 cells, while the inhibition of TPBG by siRNA in these cells significantly inhibited their proliferation accompanied by the decreased expression of cyclin D1. TPBG knockdown in KS-EMPD-1 cells also inhibited cell invasion. KS-EMPD-1 cells were also sensitive to cytotoxic agents commonly used as components of antibody-drug conjugate, a novel kind of targeted drug. These results suggest that TPBG will possibly serve as a therapeutic target for advanced EMPD.