Bortezomib downregulates the expression and production of chemokine (CXC motif) ligand 12 (CXCL12) in bone marrow stromal cells (BMSCs). BMSCs from 3 normal individuals (A, B) and 3 multiple myeloma patients (C, D) were incubated without or with bortezomib (5-500 nM) in serum-free X-VIVO medium. After 24 hr, CXCL12 mRNA levels were measured using quantitative reverse transcription-PCR (A, C). After 72 hr, media concentrations of CXCL12α were measured by ELISA (B, D). ^a)P<0.05, compared with the control (no bortezomib). (E) Serum concentrations of CXCL12α before, and 3 days after, intravenous administration of bortezomib (1.3 mg/m²) to multiple myeloma patients (N=3). ^a)P<0.05. (F) Transmigration of RPMI8226 cells induced by 3-day bortezomib-treated or -non-treated MS-5 cell culture media. ^a)P<0.05, compared with the control (no bortezomib). (G) MS-5 cell monolayers were treated with (right panel) or without (left panel) 5 nM bortezomib for 24 hr. RPMI8226 cells were added to the MS-5 monolayers, and migration of cells beneath the monolayers (the dark phases) was studied by inverted microscopy 24 hr later. Short-term bortezomib treatment inhibited the localization of RPMI8226 cells under monolayers. Representative results are shown.