Mechanically Induced Trauma Suffered by Cancer Cells in Passing Through Pores in Polycarbonate Membranes

As mechanically induced trauma to cancer cells passing through the micro-circulation may well modify their metastatic behavior, we have categorized the damage done to cultured L1210 and Ehrlich ascites tumor cells passing through 5-12 micron pores in polycarbonate membranes, as a simple, albeit limited in vitro mechanical model. It was shown that in passing through membrane pores, impaired cell reproductive integrity and 3H-thymidine incorporation were the first detected signs of trauma, followed by impaired protein synthesis (14C-labelled amino acid incorporation) and finally, impaired plasma membrane integrity (loss of trypan blue exclusion). This, together with consideration of whole cell and nuclear diameters, suggests that damage may be the consequence of traumatic spatial dissociation between components of the cell periphery, the cytoskeleton and nucleus. Following a single filtration and return to culture, there was a progressive decline in cell numbers up to 96 h. After this, the survivors remained in a 'dormant' steady state for a further 5-6 days, and only then began to divide. The induction of a 'dormant' state in cancer cells by mechanical trauma, analogous to that inflicted in the passage through the microvasculature, is as interesting as it is unexpected.