SW designed and analyzed the experiments and critically revised the drafting of the manuscript. was evaluated by in vivo mouse xenograft model. Signaling pathway involved in exosomes-treated Alpha-Naphthoflavone MSCs was detected by PCR array of human SNX14 toll-like receptor signaling pathway, RT-PCR, and Western blot. Results Data showed that lung tumor cell A549-derived exosomes could induce a pro-inflammatory phenotype in MSCs named P-MSCs, which have significantly elevated secretion of IL-6, IL-8, and MCP-1. P-MSCs possess a greatly enhanced ability in promoting lung tumor growth in mouse xenograft model. Analysis of the signaling pathways in P-MSCs revealed a fast triggering of NF-B. Genetic ablation of Toll-like receptor 2 (TLR2) by siRNA and TLR2-neutralizing antibody could block NF-B activation by exosomes. We further found that Hsp70 present on the surface of lung tumor exosomes contributed to the induction of P-MSCs by A549 exosomes. Conclusions Our studies suggest a novel mechanism by which lung tumor cell-derived exosomes induce pro-inflammatory activity of MSCs which in turn get tumor supportive characteristics. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0269-y) contains supplementary material, which is available to authorized users. for 5?min and additional 2000for 10?min to remove lifted cells. The supernatant was subjected to filtration on a 0.1-mm-pore polyethersulfone membrane filter (Corning) to remove cell debris and large vesicles, followed by concentration by a 100,000?Mw cutoff membrane (CentriPlus-70, Millipore). The volume of supernatant was reduced from approximately 250C500?mL to less than 5?mL. The supernatant was then ultracentrifuged at 100,000for 1?h at 4?C using 70Ti rotor (Beckman Coulter). The resulting pellets were resuspended in 6?mL PBS and ultracentrifuged at 100,000 for 1?h at 4?C using 100Ti rotor (Beckman Coulter). Transmission electron microscopy Purified exosomes were fixed with 1?% glutaraldehyde in PBS (pH?7.4). After rinsing, a 20-uL drop of the suspension was loaded onto a formvar/carbon-coated grid, negatively stained with 3?% (w/v) aqueous phosphotungstic acid for 1?min, and observed by transmission electron microscope. Isolation and culture of MSCs from adipose tissue Human adipose tissue was obtained from liposuction aspirates with informed consent of the Alpha-Naphthoflavone donors and was performed according to procedures provided by the Ethics Committee at the Chinese Academy of Medical Sciences and Peking Union Medical College. The isolation and culture procedures were described as previously reported . hAMSCs were resuspended in 12?ml culture medium and seeded at a density of 2??106 cells in a 75-cm2 culture flask. Cell cultures were maintained at 37?C in a humidified incubator with 5?% CO2 and passaged with trypsin/EDTA when cells were confluent. Passage 3 cells were used for following experiments. Quantitative real-time polymerase chain reaction Cultured cells were lysed by TRIzol (Invitrogen, USA), and RNA was extracted according to the manufacturers instruction. One microgram of total RNA from each sample was reverse transcribed using M-MLV (Takara) in a final volume of 20?uL. The polymerase chain reaction (PCR) amplification was carried out using the Step-one System (Bio-Rad) with SYBR Green Mastermix (Takara). All quantitative real-time PCR (qRT-PCR) results were carried out in duplicate and normalized to GAPDH. The primer of the related gene list is found in Table?2. Table 2 Primers for RT-PCR test. Differences were considered statistically significant at * em P /em ? ?0.05, ** em P /em ? ?0.01, and *** em P /em ? ?0.001. Acknowledgements This study was supported by grants from the National Natural Science Foundation of China (No. 81370466), the National Science and Technology Major Projects for Drug Research and Development (2014ZX09101042), Key Program for Beijing Alpha-Naphthoflavone Municipal Natural Science Foundation (No.7141006), National Collaborative Innovation Program (for Biotherapy), Beijing Science and Technology Project (Z151100001615063). Abbreviations ALPalkaline phosphataseAMSCsadipose tissue-derived MSCsBMSCsbone-marrow-derived MSCsEDTAethylene diamine tetra-acetic acidELISAenzyme-linked immunosorbent assayFBSfetal bovine serumFITCfluorescein isothiocyanateH-DMEMhigh glucose of Dulbeccos modified Eagles mediumHEhematoxylin-eosinHSPheat shock proteinILinterleukinJNKc-Jun N-terminal kinaseMCP-1monocyte chemotactic protein 1MSCsmesenchymal stem cellsMyD88myeloid differentiation factor.