CELL-LINES DERIVED FROM HUMAN GLIOMAS ACTIVATE MULTIPLE AUTOCRINE PATHWAYS

Fifteen permanent cell lines derived from maligant human gliomas and 5 sublines derived thereof were analyzed for the secretion of mitogenic activities. Conditioned media (c-med) from all cells were obtained from four to six day long periods of serum-free culture. The optimal conditioning time period resulting in maximal activity of the media varied between the cell lines. These conditioned media were added in final concentrations ranging from 5% to 60% to autologous and heterologous glioma cell cultures in serum-free conditions. These cultures were counted after 2, 4 and 6 days. It was observed, that there were two distinct groups of cells in respect to the response to the autologous media. 11 cell lines responded to their own c-med with dose dependent, enhanced rate of proliferation. The other cell lines proliferated in serum-free medium without response to the addition of c-med. Analyzing the responses to heterologous assays it was found, that media which did not show effect in the homologous system, were mitogenic for other cell lines. Also, cells which did not respond to their own media, responded to heterologous c-med. This study indicates, that in vitro two groups of glioma cell-lines can be distinguished in respect to the response pattern to autologous growth factors secretion. It was also seen, that the activities supporting proliferation did not act on five randomly chosen meningiomas in early culture, indicating some degree of lineage specificity. From this study it may be concluded that active growth factor secretion by tumor cells does not necessarily imply that the cells depend on such mechanism for maintenance of cell division, Furthermore, it needs to be acknowledged, that there may be a multiplicity of autocrine/paracrine growth factors secreted by individual cell lines and possibly tumors.