EARLY INTERACTIONS OF CANCER-CELLS WITH THE MICROVASCULATURE IN MOUSE-LIVER AND MUSCLE DURING HEMATOGENOUS METASTASIS - VIDEOMICROSCOPIC ANALYSIS

Biomechanical interactions of cancer cells with the microvasculature w ere studied using high resolution intravital videomicroscopy. We compa red initial arrest of murine B16F10 melanoma and D2A1 mammary carcinom a cells fluorescently labelled with calcein-AM, in low pressure (liver ) vs high pressure (cremaster muscle) microvascular beds. Cells were a rrested due to size restriction at the inflow side of the microcircula tion, penetrating further and becoming more deformed in muscle than li ver [median length to width ratios of 3.3 vs 1.3 for D2A1 cells, and 2 .5 vs 1.2 for B16F10, at 1 min post-injection (p.i.)]. During the next 2 h many cells became stretched, giving maximum length to width ratio s of 68 vs 22.1 (D2A1) and 28 vs 5.6 (B16F10) in muscle vs liver. Ethi dium bromide exclusion demonstrated that over 97% of the cells maintai ned membrane integrity for >2 h p.i. (In contrast, when an acridine or ange labelling procedure was used, membrane disruption of B16F10 cells occurred within 15 min p.i.) Our experiments do not indicate the ulti mate fate of the cancer celts, but if cell lysis occurs it must be on a time scale of hours rather than minutes. We report a process of 'cla smatosis' in cancer cells arrested in the microcirculation: large memb rane-enclosed fragments (>3 mum in diameter) became 'pinched off' from arrested cells, in both liver and muscle, often within minutes or eve n seconds of arrest. The significance of this process is not yet under stood. In this study intravital videomicroscopy has thus provided a va luable clarification of the interactions of cancer cells with vessel w alls during metastasis.