THE METASTATIC CHARACTERISTICS OF MURINE LYMPHOMA CELL-LINES IN-VIVO ARE MANIFESTED AFTER TARGET ORGAN INVASION

The ability of a tumor cell to survive is critical for successful diss emination to sites distant from the primary tumor. Tumor cells must en ter blood circulation, resist hemodynamic shear stress of the blood ci rculation, successfully extravasate, and then migrate through dense ti ssue stroma to a site favorable for tumor growth. Some tumor cells mus t therefore be endowed with peculiar abilities to successfully metasta size, whereas others, although capable of forming tumor in specific or gans, cannot metastasize. This property has often been associated with the homing ability of a given tumor cell, likely through the expressi on of organ-specific homing receptors that are critical for the extrav asation process. The present work was aimed at establishing the point at which metastatic and nonmetastatic lymphoma cells diverge. Although 164T2 and 267T2 lymphoma cell lines can successfully form thymic lymp homa when injected intrathymically, only the 164T2 clone can efficient ly form tumor in kidneys, spleen, and liver after intravenous inoculat ion. Using the Indium-labeling technique to monitor the homing kinetic of both cell lines, we showed that the critical step for the successf ul metastasis of the lymphoma cell was determined in the final steps o f the disseminating process, namely after homing. These results indica te that, whereas binding of tumor cells to vascular endothelium throug h specific adhesion mechanisms is a prerequisite for dissemination of tumor cells, the resistance of a tumor cell to the antagonist action o f the host and/or its ability to grow tumor occurs only after homing t o the target organ. (C) 1998 by The American Society of Hematology.