Heterogeneity of murine mammary adenocarcinoma cell subpopulations. In vitro and in vivo resistance to macrophage cytotoxicity and its association with metastatic capacity.

Properties of Ts, a long-term tissue culture line of T1699 mammary adenocarcinoma of DBA/2 mice, and two of its sublines - TR2 and TLI-1-were comparatively studied. Ts tumors produced no spontaneous metastases, nor did i.v. injection of up to 1 X 10(6) Ts cells produce a lung tumor nodule. Ts cells were susceptible to macrophage cytotoxicity in vitro and i.v. injected cells were rapidly destroyed in the lungs. TLI-1 tumors spontaneously metastasized to the lungs, and i.v. injection of 1 X 10(3) TLI-1 cells produced approximately 15 lung nodules per animal. TLI-1 cells were least susceptible to both macrophage-mediated cytolysis in vitro and in vivo host antitumor mechanisms. TR2 cells were intermediate with respect to all these properties. Differences in their susceptibility to macrophage cytotoxicity were recognized not only by normal peritoneal macrophages but also by murine macrophage lines. On the other hand, all the subpopulations were uniformly resistant to NK activity in vitro. These findings suggest that resistance of tumor cells in vitro to macrophage cytotoxicity corresponds with their in vivo metastatic potential.