Experimental neovascularization in vivo: the early changes in a stable adult vasculature responding to angiogenic stimulation by a syngeneic neoplasm.

To examine the vascular changes that lead to the development of new vessel sprouts from differentiated vessels the early response of an uninjured, stable, adult vascular bed to the presence of neoplastic tissue has been studied. Small grafts of a squamous cell carcinoma were implanted above the cremaster muscle of host rats syngeneic with the rat in which the neoplasm arose. The vascular response was examined by light microscopy of whole cremaster preparations after intravenous injection of colloidal carbon to label leaky vessels, and by scanning electron microscopy of methyl methacrylate injection casts. Three to five days after implantation there was a dramatic increase in the number of visible blood vessels of the microcirculation adjacent to the graft as a result of altered blood flow through the existing microvasculature. Capillaries and post-capillary venules became widely distended, tortuous and variably permeable to the introduced colloidal marker. Capillary involvement was restricted to the area nearest the graft while post-capillary venules were affected in more remote regions. Networks of newly formed vascular channels developed from the extremities of the tortuous loops. Altered permeability within the pre-existing vessels was related to the distension and tortuosity, with a pattern of vascular labelling quite unlike that induced by inflammatory mediators or tumour secreted vascular permeability mediator (VPM). These changes are considered to be the result of altered inter-endothelial cell adhesion and cellular rearrangement, and represent important antecedent stages in the formation of the new vascular structures.