ObjectiveTo study the cellular localization of a novel human thrombospondin R-spondin 3 and its role in the development and progression of tumors.MethodsThe subcellular localization of R-spondin 3 was investigated in HEK293 cells by fluorescence micrography. Colon carcinoma cell lines HT-29 and LoVo were transfected with pcDNA-Rspo 3 recombinant expression plasmid; and the cell cycle and apoptosis were detected by Flow Cytometry (FCM). Cell adhesion and invasion ability were determined by Matrigel reagents and Transwell system, respectively.ResultsFluorescence micrography showed that EGFP-Rspo 3 fusion protein was mainly localized in nuclei as dispersed particles. Overexpression of R-spondin 3 showed no effect on cell cycle in both colon carcinoma cell lines. Overexpression of R-spondin 3 induced apoptosis of LoVo cells with high malignancy (P<0.01) although it showed no effect on the apoptosis of HT-29 cells with low malignancy. The overexpression also promoted the adhesion ability (P<0.01), restrained invasion ability (P<0.01) and motility of both colon carcinoma cell lines.ConclusionOur research indicates that R-spondin 3 localize in the nuclei; it can induce apoptosis and restrain metastatic potential of some tumor cells.