Abstract 5164: Mesenchymal stromal cells promote tumor engraftment and progression in tumor xenograft model

Mouse transplantation model for in-vivo characterization of human tumor cells exhibits variable and lower tumor-taking efficiency for primary human tumors than immortalized cancer cell lines. Tumor microenvironment has been well recognized to have important role for tumor proliferation and metastasis. However, little is known about potential influence of species-specific microenvironment for human and mice model. Here, we investigated the impact of species-barrier for tumor engraftment and evaluated effects of matrigel and mesenchymal stromal cell (MSC) as a potential factor that can influence tumor microenvironment. First, identical CFC-equivalent number (1x104) of mouse sarcoma cell (WEHI164) and rat sarcoma cell (RR1022) were injected subcutaneously into NOD/SCID IL2rg−/− (NSG) mice and immuno-suppressed rat (Sprague Dawley, treated with FK506 and Dexamethasone 1 mg/kg/day, each, ip). RR1022 showed earlier and superior tumor development to those of WEHI164 in rat (P=0.006), whereas, no significant difference in NSG mice (P=0.50). Subsequently, both sarcoma cells (1x104 CFC equivalent) were injected with matrigel, WEHI164+matrigel showed superior tumor development to WEHI164 alone in rat (P=0.035), but not in NSG mice. Moreover, matrigel didn't show advantage for RR1022 in both rat and NSG mice. Next, we investigated the effect of human-MSCs on human sarcoma cells (HT1080) growth by using co-culture system. HT1080 cells co-cultured with/without transwell showed 1.3 times and 1.8 times (respectively) more rapid growth than HT1080 cells alone at day 6. When HT1080 cells (1x105) were injected with matrigel, human-MSC or rat-MSC into rat, tumor development were detected in 100% (6/6, each group) at day 14. However, HT1080 cells with human-MSC showed greater tumor volume than those with matrigel (P=0.03) and rat-MSC (P=0.04). In addition, on microscopic examination, tumors from HT1080 co-injected with human-MSC or rat-MSC showed infiltrative growth pattern with desmoplastic reaction, which were not observed in HT1080 alone or HT1080 with matrigel. Similar findings were observed in another set of experiment, 5FU cells (human gastric cancer cell line) co-injected with human-MSC into NSG mice showed infiltrative growth and lung metastasis, whereas 5FU cells alone showed only expansile growth pattern without lung metastasis. In conclusion, our results suggest that the microenvironmental species-barrier may exist and that human-MSCs would have tumor promoting effe