Arrest and extravasation of B16 amelanotic melanoma in murine lungs. A light and electron microscopic study

Abstract

The arrest and extravasation of tail vein-injected B16 amelanotic melanoma (B16a) cells, disaggregated from subcutaneous tumors, were studied at intervals from 10 minutes to 5 days in lungs of C57BL6J mice. Tumor cells were found in the pulmonary vasculature at 10 minutes postinjection and were commonly associated with platelets and fibrin. Tumor cells with associated thrombi increased, reaching a peak at 4 hours. Arrest of the B16a melanoma tumor cells appears to involve contact with endothelial plasma membrane, often with adjacent but not interposed platelet and fibrin thrombus formation. The tumor cell-associated thrombi subsequently decreased in frequency and were rarely found after 48 hours. The arrested tumor cells were initially in contact with the endothelial cells, which were gradually displaced by tumor cells achieving contact with the vascular basal lamina (BL). Initial contact with the vascular BL was observed at 4 hours, with a progressive increase in contact over the subsequent 2 days. Blood flow was commonly reestablished past the BL-attached tumor cells after dissolution of the thrombi. Mitotic figures in the tumor cells attached to the BL were frequent after 24 hours and the tumor appeared to proliferate intravascularly along the basal lamina. Penetration of the BL by tumor cell cytoplasmic processes was first observed at 3 days with continued dissolution of the vascular BL developing through day 5. Extravasation occurred through a combination of intravascular tumor cell proliferation and destruction of vascular BL by the B16a cells. Migration or diapedesis of the tumor cells was not observed in any of the time periods studied.