MAMMARY-CARCINOMA CELL-LINES OF HIGH AND LOW METASTATIC POTENTIAL DIFFER NOT IN EXTRAVASATION BUT IN SUBSEQUENT MIGRATION AND GROWTH

We examined the extravasation and subsequent migration and growth of m urine mammary tumor cell lines (D2A1 and D2.OR) which differ in their metastatic ability in lung and liver, invasiveness in vitro and expres sion of the cysteine proteinase cathepsin L. In light of the differenc es in invasiveness and cathepsin L expression, we hypothesized that du ring hematogenous metastasis the two cell lines would differ primarily in their ability to extravasate. We used in vivo videomicroscopy of m ouse liver and chick embryo chorioallantoic membrane to examine the pr ocess and timing of extravasation and subsequent steps in metastasis f or these cell lines. In contrast to our expectations, no differences w ere found between the cell lines in either the timing or mechanism of extravasation, at least 95% of cells having extravasated by 3 days aft er injection. However, after extravasation, the more metastatic and in vasive D2A1 cells showed a greater ability to migrate to sites which f avor tumor growth and to replicate to form micrometastases. These stud ies point to post-extravasation events (migration and growth) as being critical in metastasis formation,