Soluble factors released by the target organ enhance the urokinase-type plasminogen activator activity of metastatic tumor cells

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Abstract
The ability of tumor cells to respond to microenvironmental factors present in the target organ may be necessary for successful metastasis. Many studies suggest that urokinase-type plasminogen activator (u-PA) has a significant role in several steps of the metastatic process. In previous work it had been observed that lung conditioned media stimulated the migration and growthin vitro of cells from a murine mammary adenocarcinoma (M3) with moderate lung metastasizing potential. In the same experiments liver conditioned medium exerted a marked cytostatic effect on M3 cells. The aim of the present work to investigate whether conditioned media from lung, kidney or liver, were able to modulate u-PAin vitro secretion by these murine M3 cells. Secreted u-PA measured by fibrinolytic assay, was significantly increased only when M3 primary cultured cells were treated for 24 h with lung conditioned media prepared from normal mice or from mice bearing a small tumor. Exposure to kidney or liver conditioned media did not modify the u-PA secretion pattern already shown by the tumor cells. The activity shown by lung conditioned media seemed to be specific for these syngeneic tumor cells, as no effect was observed on murine embryo cells. These results suggest that soluble factors released by the target organ could specifically induce tumor cellsin vivo to enhance the production of degradative enzymes, thus facilitating the last steps of the metastatic cascade.