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Intercellular transfer of P-glycoprotein from the drug-resistant human bladder cancer cell line BIU-87 does not require cell-to-cell contact.

J Urol. 2013 Apr 22;

Authors: Zhou HL, Zheng YJ, Cheng XZ, Lv YS, Gao R, Mao HP, Chen Q


PURPOSE: The efflux activity of transmembrane P-glycoprotein (P-gp) prevents a variety of therapeutic drugs from reaching lethal concentrations inside cancer cells, resulting in multidrug resistance. In this study, we investigate whether drug-resistant bladder cancer cells can transfer functional P-gp to sensitive parental cells. METHODS: Drug-sensitive bladder cancer cells (BIU-87) were co-cultured for 48 h with an adriamycin-resistant derivative of the same cell line (BIU-87/ADM) in a transwell system that prevented cell contact. The presence of P-gp in membranes of recipient cells was established using FITC, LSCM, and western blotting. P-gp mRNA levels were compared between all cell types. Rhodamine 123 efflux assay was carried out to confirm that P-gp was biologically active. RESULTS: The amount of P-gp protein in BIU-87 cells co-cultured with BIU-87/ADM was significantly higher than in BIU-87 cells (0.44 vs. 0.25, P < 0.001) and BIU-87/H33342 cells (0.44 vs. 0.26, P < 0.001), indicating P-gp transfer. P-gp mRNA expression was significantly higher in BIU-87/ADM cells than in co-cultured BIU-87 (1.28 vs. 0.30; P < 0.001), BIU-87/H33342 (0.28), and BIU-87 cells (0.25) (P < 0.001), ruling out a genetic mechanism. After 30 minutes of efflux, the fluorescence intensity of Rh123 was significantly lower in BIU-87/ADM (5.55 vs. 51.45; P = 0.004) and co-cultured BIU-87 cells than in BIU-87 cells (14.22 vs. 51.45; P < 0.001), indicating the P-gp was functional. CONCLUSIONS: Bladder cancer cells can acquire functional P-gp through a non-genetic mechanism that does not require direct cell contact. This mechanism is thus consistent with a microparticle-mediated process.

PMID: 23618585 [PubMed - as supplied by publisher]