Incipient Angiogenesis

Extract

The hypothesis that tumor growth is angiogenesis dependent (1,2) was first proposed in 1971 based on observations that expansion of a tumor mass was limited in the absence of angiogenesis. Since then, considerable experimental supporting evidence for this concept has been assembled from inhibition of angiogenesis by the following observations: 1) mechanical separation of tumor cells from their nearest vascular bed (3), 2) blockade of tumor-derived angiogenic factors (4), 3) administration of angiogenesis inhibitors (5), 4) blockade of endothelial receptors for angiogenic factors (6), 5) endogenous production of angiogenesis inhibitors from tumor cells (7,8), and 6) demonstration of the preangiogenic phenotype in spontaneous tumors (9). The size limits of experimental tumors when angiogenesis is blocked or absent are between approximately 0.2 mm in diameter [for lung metastases in mice (10)] and 2 mm, i.e., a tumor population of 10⁵-10⁶ cells (for avascular chondrosarcomas in rats [Fang J, Shing Y, Wiederschain D, Yan L, Butterfield C, Jackson G, et al.; unpublished results]). The differences in size of avascular preangiogenic tumors may be due in part to the capacity of tumor cells to survive under differing degrees of hypoxia (11).