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Pieces of the endothelium of the aorta of BDX rats were confronted with two syngeneic-tumor-cell variants. While the AS variant is non-metastasizing, the ASML cells metastasize spontaneously via the lymphatic vessels. By means of scanning-electron microscopy the adhesion phenomena and the various stages of invasive activity of the non-metastasizing variant (AS) as well as the retraction of the endothelial cells depending on the time of confrontation were studied. Though the metastasizing variant (ASML) adhered firmly to the endothelium, we found neither signs of invasive activity of these tumor cells nor retraction phenomena of the endothelial cells. Aggregates of AS- and clusters of ASML-cells, respectively, behaved in exactly the same way as single cells: while the ASML-clusters remained inactive, the AS-aggregates exhibited invasive activities. Those cells which were in intimate contact with the endothelium started to leave the aggregate, thereby forming a foot-like layer beneath the rest of the aggregate; these cells began to invade.

In continuation of a previous paper (1), we have prolonged the time of confrontation of two rat tumor cell variants (BSp73 AS and ASML) with normal epithelial cells and broadened the spectrum of confrontation partners. In addition to the aorta we have also used small veins, the ductus thoracicus as a lymphatic vessel, the diaphragm, and lung fragments. The organ sections were preserved for a longer period of time by incubating them in a gyratory shaker. Under these conditions the vessel material and diaphragm remained morphologically intact for up to 12 hrs; lung cubes concealed the cut surfaces by immediate wound healing, and were preserved intact for up to 40 days. All endothelia and the mesothelium of the diaphragm were destroyed by the nonmetastasizing AS cells, but the basal lamina remained intact by morphological criteria even after 18 hrs of exposure to the AS cells. The metastasizing ASML cells attached by filopodia mostly to the basal lamina of the vessels, but were unable to destroy neither the endothelia nor the basal lamina. The superficial cell layers of the lung cubes, however, were penetrated by the cells of both tumor lines, but to a different degree.

The colonization of the lung by the rat tumor cells BSp73 ASML which have the ability to metastasize via the lymphatic system was studied at the ultrastructural level. Tumor cells arriving in the lung after i.v. injection become transiently embolized; within hours, however, they begin to extravasate from the blood capillaries. Swelling cellular protrusions open a limited area between endothelium and basal lamina through which tumor cells erupt. Tumor cells then form metastases in the interstitial tissue and, in an apparently lymphotropic action, intravasate the lymphatic vessels in a similar manner to a reverse diapedesis-like process. Within the lympatic system they settle, spread, and build up extensive tumor foci particularly in the subpleural region.

Serum of patients with small cell lung cancer as well as serum fractions recovered by column chromatography inhibit the in vitro antibody synthesis in a PWM driven lymphocyte culture system and the capacity of T-lymphocytes to form rosettes with sheep erythrocytes. Utilizing an in vitro antibody synthesis system recomposed of previously separated B-cells and T-helper cells, we could show that the inhibiting high-molecular weight factors (between 40,000 to 60,000 dalton) from the patients' serum are suppressing antibody synthesis by inactivation of T-helper cell function. The mechanisms of inhibition are still unclear. The factors inhibiting E-rosette formation which are in the molecular weight range of 10,000 dalton and lower are not the same as the factors suppressing the antibody production.