Morphological Study of the Interaction of Intravascular Tumor Cells with Endothelial Cells and Subendothelial Matrix

Multiple steps or events have been described as essential in the metastatic cascade. Tail vein injection of single cell suspensions was used to study the ultrastructural details of the events involved in the initial arrest and attachment of circulating tumor cells. Lewis Lung Carcinoma (3LL) and a mammary adenocarcinoma (16c) were compared to a previous ultrastructural study of B16 amelanotic melanoma (B16a) detailing morphological events in the initial arrest and attachment of tumor cells in lung. The three murine tumors followed similar steps and varied only slightly in the time sequence of the steps. We observed the following steps: (a) initial arrest of tumor cells was characterized by an intimate tumor endothelial cell contact; (b) platelet activation and aggregation was noted by two minutes. Platelet aggregation continued for 1-4 h until a thrombus formed; (c) after approximately 4 h endothelial cell separation with extension of the tumor cell to the subendothelial matrix was noted; (d) at approximately 24 h the tumor cell associated thrombus dissipated and the attached tumor cells were exposed to a reestablished circulation. (e) mitoses were observed after 24 h with cell division and the development of intravascular tumor nodules; (f) the final step in the extravasation sequence was dissolution of the basement membrane by the attached tumor cells.