Inhibition of lung colonization at two different steps in the metastatic sequence

Abstract

Two immunomodulatory protocols were evaluated for their ability to inhibit lung colonization by mouse mammary tumor line 4T07. Preimmunization with tumor cells or pretreatment with poly I:C were equally effective at inhibiting lung colonization but a clonogenic tumor cell assay demonstrated that the treatments reduced tumor cell burden at different steps during the metastatic process. Poly I:C pretreatment accelerated tumor cell clearance based on the recovery of clonogenic tumor cells from lungs dispersed within 6 h post-arrest. Preimmunization inhibited the subsequent replication of tumor cells which survived and established in the lung, as indicated by the expansion of clonogenic cell numbers between 1 day and 7 days post-arrest. Histologic examination of serial sections of lungs demonstrated that very few (6%) of the tumor cells were extravascular 6 h post-tumor cell injection. By 24 h and 168 h the percentages of tumor cells which were extravascular had increased to 62% and 86%, respectively. Thus, poly I:C pretreatment appears to enhance killing of tumor cells prior to extravasation, whereas preimmunization appears to inhibit tumor cells after extravasation.