Tumoral Vascularity: What Does It Tell Us About the Growth and Spread of Cancer?

Abstract

Without blood vessels, tumor cells continue to grow until passive diffusion no longer allows enough nutrients to enter or metabolic waste products to exit (1–17). Furthermore, intratumoral endothelial cells proliferate faster than those in the adjacent benign stroma (45-fold faster in breast carcinoma and 30-fold in prostate carcinoma) (18, 19), and the rate of tumor progression increases with increased intratumoral vascularity (19–92). Also, different techniques to specifically inhibit angiogenesis (i.e., not cytostatic to tumor cells in vitro) clearly inhibit tumor growth in vivo (93–104). For example, an analog of fumagillin (a.k.a. AGM-1470 or TNP-470) inhibits endothelial proliferation in vitro and tumor-induced angiogenesis in vivo (95) TNP-470 and other angiogenesis inhibitors are now in various phases of clinical trials as therapeutic agents for a variety of malignant solid tumors, leukemias, and infantile hemangiomas (1,93,94). Moreover, Kim et al. (97) found that inhibition of vascular endothelial growth factor (VEGF)-induced angiogenesis suppressed tumor growth in vivo. This group injected human malignant cell lines into nude mice followed by treatment with a monoclonal antibody specific for VEGF. The antibody inhibited the tumor growth and reduced tumor vessel density, but had no effect on the growth rate of the tumor cells in vitro. Millauer et al. (99) noted marked suppression of tumor growth with the introduction of defective VEGF receptors into tumor endothelial cells. He also noted that a single intravascular injection of antagonists of the ν3 integrin disrupted ongoing angiogenesis in the chick chorioallantoic membrane.