Clinical efficacy of n-3 PUFAs for the treatment of NAFLD/NASH is still controversial

nes upon co-culturing. B) Two out of the 7 of the lung cancer cell lines exhibited a significant increase in cell survival upon co- culturing with MRC5 cells; out of which the H596 cells exhibited the greatest fold-change in proliferation upon co-culturing. C) Of the two breast cancer cell lines that exhibited an increase in proliferation upon co-culturing with MRC5 fibroblasts, only the BT20 cells exhibited a significant increase in cell survival. doi:10.1371/journal.pone.0127948.g003 The lung cancer cells, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19666584 exhibited no significant reduction in survival when treated with Erbitux, mAb IL6 or mAb IGF1R in monoculture. In co-culture with MRC5 cells or primary lung TAFs a significant reduction in survival was observed upon treatment with mAb cMet, but not with the PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19666601 other therapeutic agents used. The survival of the breast cancer cells in co-culture with MRC5 cells was significantly reduced upon treatment with by mAb IL6. This effect was not observed when the BT20 cells were in monoculture. Treatment with Erbitux, mAb cMet or mAb IGF1R did not influence the survival of BT20 cells in monoculture or co-culture with corresponding fibroblasts. Discussion Although it is evident that tumor-stroma crosstalk appears to play a critical role in tumor progression, and resistance to therapeutic agents, few suitable in vitro tools/models are available to examine these interactions. Most of the in vitro data regarding the efficacy of therapeutic agents have been obtained from 2D mono-cultures of cancer cells in which the stromal component is lacking or from trans-well systems in which the tumor cells and stromal cells are physically separated. Alternatively, in vivo data have been obtained from xenograft models in which human tumor cells interact with mouse stromal cells. However, this microenvironment, if at all, is a poor substitute for the human TME. These in vitro and in vivo methods may overestimate the effects of therapeutic agents, in contrast to co-culture models in which human tumors cells and fibroblasts of human origin directly interact with each other. The co-culture model we described in this study involves culturing tumor cells and fibroblasts in a 3D setting that mimics the in vivo micro-environment. This model enables the monitoring of the effects of coculturing and the contribution of the crosstalk between tumor cells and fibroblasts in vitro in the absence of exogenous factors, such as serum, growth factors or hormones, on cell survival. Our data from the experiment comparing trans-well based co-cultures and 2D co-cultures to 3D co-culture model clearly indicated that 3D co-culture exerts a differential impact on cell survival. Using this model, we revealed for the first time that different cancer cell types MedChemExpress Vonoprazan elicit distinct sets of secreted factors from stromal fibroblasts and, thus, can uniquely influence cell survival and therapeutic responses to therapeutic agents. We used cancer cells from different tumor types and FAP-positive fibroblasts from different origins, including primary TAFs, for the co-culture experiments. Upon dissociation of spheroids on day 5 to identify the proliferating population, we found that the predominant proportion of the proliferating cells in the co-cultures was cancer cells . However, co- culturing with fibroblasts did not induce enhanced proliferation of all cancer cell lines tested. In fact, there were some cell lines that proliferated either equally well or better as mono-cultures indicating that there m