Malignant mouse melanoma cells do not form tumors when mixed with cells of a non‐malignant subclone: Relationships between plasminogen activator expression by the tumor cells and the host's immune response

Abstract

Mouse melanoma clones B₅59 and B78 are highly tumorigenic when injected into C57BL/6J mice. Tumor formation by these cells is suppressed when they are mixed with nonmalignant bromodeoxyuridine‐grown clone C₃471 before injection. C₃471 cells suppress tumor formation only in immunocompetent hosts; mixtures of B₅59 and C₃471 cells or C₃471 cells alone form tumors in antithymocyte serum (ATS)‐treated mice. Explants of C₃471 tumors grown in ATS‐treated mice form tumors in immunocompetent mice, most of which regress. Inability of C₃471 or mixtures of C₃471 with malignant cells to grow in normal mice, as contrasted with ability to grow in immunosuppressed mice, indicates that host response is involved. Both tumorigenic clones have high plasminogen activator activity, whereas nontumorigenic clone C₃471 has none. Mixture of either tumorigenic clone with C₃471 cells decreases plasminogen activator in vitro. C₃471 tumor explants from ATS‐treated mice initially express plasminogen activator, but lose the capacity to express this activity upon prolonged cultivation in vitro. Explants from B₅59 tumors retain plasminogen activator in long term culture. Close physical contact between C₃471 and B₅59 cells appears essential both for inhibition of plasminogen activator expression by B₅59 cells in vitro, and for tumor suppression in vivo. These findings suggest that production of plasminogen activators by tumor cells may play an important role in suppressing the host's immune response locally to an inoculum of syngeneic tumor cells.