Invasion of endothelial cell monolayers on collagen gels by cells from mammary tumor spheroids.

Suspensions of multicellular mammary tumor spheroids (MTS) were allowed to interact with confluent monolayers of endothelial cells cultured on top of collagen gels. A number of early and late interactions between MTS and endothelial cell monolayers occurred. The early phase was characterized by the attachment of MTS to the culture and retraction of endothelial cells near the attached spheroid. Only these early interactions were observed up to 8 hr after addition of the MTS. Thereafter, cells from MTS migrated away from the spheroids. The late phase was characterized by cells of the MTS spreading on top of the collagen gel, moving underneath the edges of the endothelial cells, extending as cords of cells on top of the endothelium, and invading into the collagen matrix. During both the early and late phases, cells from the MTS were distinguished from the endothelial cells by the intense staining of tumor cells with Giemsa and the presence of microvilli found only on tumor cells. Attached MTS, which were noted at 2 hr after addition (the earliest time examined), increased in number for up to 12 hr. Polyionic compounds known to affect cell surface charge were found to reduce the numbers of attached MTS. The results demonstrate that the system described in this study can provide a useful model for analyzing the mechanisms of tumor embolus interaction with blood vessel walls.