Mechanical aspects of the lungs as cancer cell-killing organs during hematogenous metastasis.
A substantial proportion of many different types of circulating cancer cells appear to be killed during their interactions with the pulmonary microcirculation. Different tensions exist during respiration within alveolar units, and hence the pulmonary capillaries. We have calculated the effects of these tensions on the entry and subsequent fate of circulating cancer cells. Our calculations indicate that during expiration, when tension in the capillary walls is low, cancer cells can enter and travel along the capillaries without damage, because the vessels are deformed by the cells and the hydrodynamic field surrounding them. During normal inspiration when the alveoli are stretched, the increased tension within the capillary walls serves to compress the contained cancer cells. This compression, together with previously calculated blood pressure differentials between the ends of the cells, is thought in some cases, to increase their membrane tensions above the critical level for rupture, resulting in cytolysis, in accord with experimental observations. In deep inspiration, when a very substantial increase in capillary wall tension occurs, cancer cells already within the capillaries, entering them and in transit along them are expected to develop membrane tensions greatly exceeding the critical values for rupture. It is suggested that these respiration-induced effects may act as an important rate-regulating step in the metastatic process, where the development of pulmonary metastases plays a central role. Furthermore, induced deep inspiration may conceivably be utilized in the inhibition of pulmonary metastasis.
D000818:Animals; D002196:Capillaries / Q000502:physiology; D002462:Cell Membrane; D002470:Cell Survival; D008114:Liver Neoplasms, Experimental / Q000503:physiopathology; D008168:Lung / Q000502:physiology*; D008833:Microcirculation / Q000502:physiology; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009360:Neoplastic Cells, Circulating; D011652:Pulmonary Circulation; D051381:Rats; D012119:Respiration; D013499:Surface Properties