Tumours acquire their vasculature by vessel incorporation, not vessel ingrowth

This study was designed to investigate the early development of tumour circulation using a transplantable mouse mammary adenocarcinoma. Tumour cells (10(6] were injected subcutaneously into the flank and groups of treated mice were killed at 24 h intervals up to 12 days; the tumours and surrounding tissues being processed by standard histological methods. Sections of tumour were sub-divided into neoplastic tissue, vessels and connective tissue using computer-assisted morphometric techniques: the host tissue around the tumour was similarly quantified for vessels and connective tissue. With increasing tumour size, the proportion of vessels within tumours rapidly increased to reach a plateau of approximately 1.5 per cent of tumour volume, a 400 per cent increase on the vascular density of normal subcutaneous tissue. Within tumours, vascular density was always higher at the periphery than the centre. The most pronounced increase in vascular density affected the host tissue around the tumour. It is not clear why vascular development is most prominent outwith the tumour when postulated angiogenic factors, such as tumour angiogenesis factor, are presumably released within. Our results imply, however, that tumours acquire their vasculature by infiltration into, and expansion between, a network of newly formed vessels in the surrounding connective tissue.