Neovascularization induced by intraocular xenografts of normal, preneoplastic, and neoplastic mouse mammary tissues.

The capacity to induce neovascularization was compared in normal, preneoplastic, and neoplastic mouse mammary tumors from strains with a high incidence of tumors (C3H, C3H-Avy, C3H-AvyfB) by implantation of small biopsy fragments on the iris surface in New Zealand White rabbits. Proliferation of iris blood vessels was studied by: 1) direct, in vivo slit-lamp stereomicroscopy and fluorescein angiography; 2) filling of the microvasculature with colloidal carbon; and 3) histologic examination. Ninety percent of mammary tumor implants elicited iris neovascularization after 48-72 hours, regardless of their histologic classification or the presence or absence of mammary tumor virus. Corticosteroid treatment reduced immediate postoperative inflammation (12-36 hr) but did not abolish subsequent growth of new vessels. Necrotic tumor fragments failed to elicit any neovascular response. In contrast, only 6% of normal tissues from resting mammary glands caused any vasoproliferation. Hormone-stimulated mammary tissues from pregnant and lactating mice exhibited a transient neovascular capacity that was lost during postweaning involution. Of the implants from premalignant hyperplastic alveolar nodules (HAN's), 30% produced a pattern of vessel growth similar to that of tumor implants. D-1 line (HAN outgrowth) tissues, which have a predicted low incidence of tumors, induced significantly fewer neovascular responses (P less than 0.002) than morphologically and biochemically similar D-2 line tissues, which have a predicted high incidence of tumors. These data suggest that the capacity to induce neovascularization is acquired during malignant progression of mouse mammary tissues; therefore, demonstration of this property may be useful in the identification of those intermediate populations most at risk for neoplastic transformation.