The significance of free blood in liquid and solid tumours.

Impregnation of the vasculature with ink was used to study microvascular changes induced in rats by liquid (ascites) and solid growth of W256 and Y-P388 tumour cells. Ascites fluid produced by both tumours was heavily blood-stained; the deep red colour of solid tumour deposits was similarly due to the presence of free blood. In both types of tumour growth this free blood was due to diapedesis of erythrocytes through tips of capillary sprouts which grow when neovascularization (angiogenesis) occurs in response to any suitable (non-neoplastic or neoplastic) stimulus. Ascites growth of these tumours induced profuse sprouting from the peritoneal capillaries; this sprouting, together with the "bleeding" it caused, were inhibited by local pre-irradiation of the peritoneal vasculature with X-rays before intraperitoneal inoculation of rats with the tumours. Similar angiogenesis with bleeding did not occur following inoculation with an allogeneic tumour in rats which had been previously immunized against the tumour. LI tumour cells (tumour cells lethally irradiated in vitro to destroy their proliferative integrity, but which remain metabolically active) also induced sprouts to grow in close proximity to the implanted LI cells, but heat-killed tumour cells caused no sprouting. The nature and significance of neovascularization of tumours and their so-called "haemorrhagic" growth are discussed.