Angiogenic capacity of preneoplastic lesions of the murine mammary gland as a marker of neoplastic transformation

Abstract

The angiogenic capacity of normal, preneoplastic, and neoplastic murine mammary tissues from high-tumor-incidence strains (C3H, C3H-AVV, C3H-AVVfB) was compared by implanting small biopsies on the iris surface in New Zealand White rabbits. Proliferation of iris blood vessels was studied by: (a) in vivo slit-lamp stereomicroscopy and fluorescein angiography; (b) colloidal carbon injection of the microvasculature; and (c) histological examination. Ninety % of mammary tumor implants elicited neovascular changes after 48 to 72 hr, regardless of their histological classification or the presence or absence of mammary tumor virus. Corticosteroid treatment did not abolish this response. In contrast, only 6% of implants from normal mammary glands caused any vasoproliferation. Thirty % of implants from premalignant hyperplastic alveolar nodules produced a pattern of vessel growth similar to tumor implants. D-2 line (hyperplastic alveolar nodule outgrowth) tissues, which have a high predicted tumor incidence, induced significantly more neovascular responses (p less than 0.002) than do morphologically and biochemically similar D-1 line tissues, which have a low predicted tumor incidence. These data suggest that angiogenic capacity is expressed during the malignant progression of murine mammary tissues; this property may provide a means for identifying those preneoplastic tissues that are most at risk for cancer.