Angiogenesis Induction by Tumors, Embryonic Tissues, and Lymphocytes

Summary Although it is well established that tumors can induce endothelial cell mitosis and angiogenesis leading to extensive neovascularization, little is known concerning the spectrum of normal cells or tissues that may have similar inductive capabilities. A variety of developmentally active tissues were tested: mouse embryonic organ rudiments, mouse and rabbit trophoblast and placenta, and blastemal fragments obtained from regenerating deer antlers. Assays for angiogenesis included grafts made to the chorioallantoic membrane of chick embryos and grafts placed intracorneally in adult rabbit eyes. Virtually all of these test tissues were negative, the only exceptions being some antler grafts and some grafts obtained from metanephric tubules of the embryonic mouse kidney. In contrast, a striking vascular reaction could be evoked by foreign lymphocytes obtained from spleen or lymph node. Originally examined by intradermal inoculation into adult allogeneic mice, competent lymphocytes were shown to evoke extensive vascular responses in host animals, characterized by increased visualization of blood vessels, vascular divarication, and marked endothelial cell activity. When tested in the chick chorioallantoic membrane assay, mouse lymph node and spleen cells induced a typical angiogenesis response, and, similarly, mouse lymph nodes as well as allogeneic rabbit lymph nodes elicited the characteristic neovascularization reaction when grafted intracorneally into adult rabbits.