Endothelialization of embolized tumor cells during metastasis formation.

The reaction of the endothelial barrier to tumor cell extravasation has been studied using electron microscopy. The model system was pulmonary metastases produced by intravenous injection of B16-F10 melanoma cells. A striking difference was observed in the behavior of the endothelial lining of arterioles versus that of capillaries. In capillaries, partial retraction of endothelial cells took place following the attachment of tumor cells. The tumor cells then immediately attached to the basement membrane and the basolateral surface of the retracted endothelial cells. The endothelial cells extended to cover the tumor cells prior to complete extravasation. In the arterioles, on the other hand, endothelial retraction did not occur following tumor cell attachment. Instead the attached tumor cell emboli became encompassed by endothelial cells, outgrowing from the intact endothelial lining of the arteriole. Owing to the proliferation of the tumor cells, tumor colonies encompassed by endothelial cells expanded within the lumen. When these intravascular growths completely filled the lumen, the tumor cells extravasated from the vessel only after the original endothelial layer became mechanically disrupted and the tumor cells thereby came into contact with the basement membrane.