hXBP1s overexpression in BMSCs enhances their support of MM cell growth and bone resorption in vivo. (A) Western blot demonstrating that lentiviral infection of Flag-hXBP1s led to enhanced expression of hXBP1s in KM101 cells. EV-expressing lentiviruses did not induce endogenous XBP1s protein level and phosphorylation of IRE1α in the KM101 cells (top). RFP fluorescence images indicate high infection efficiency (bottom). (B) Overexpression of XBP1s in KM101 cells enhanced MM cell growth in SCID mice. The tumor growth at 4 weeks after injection was reflected by fluorescence imaging of GFP. White arrows indicate MM tumor masses formed by the injected 5TGM1-GFP-TK cells. One of 4 representative mice is shown for each group. (C) ELISA analyses demonstrating the serum concentrations of IgG2b in the injected SCID mice before and after cell injections at 4 weeks after injection (n = 3; mean ± SD; *P < .05. NS indicates not statistically significant. (D) μQCT analysis demonstrating more severe and extensive osteolytic lesions in the SCID mice with XBP1s-KM101 cells plus GFP-5TGM1 cells compared with those with EV-KM101 plus GFP-5TGM1 cells. Black arrows indicate bone destruction.