TUMOR DORMANCY IN VIVO BY PREVENTION OF NEOVASCULARIZATION*

TUMOR DORMANCY IN VIVO BY PREVENTION OF NEOVASCULARIZATION*

VOLUME 136, 1972 | BY MICHAEL A. GIMBRONE, JR., STEPHEN B. LEAPMAN, RAMZI S. COTRAN,‡ AND JUDAH FOLKMAN§
This study investigates the relationship between neovascularization and the growth of solid tumors. The authors propose that tumor angiogenesis factor (TAF), an endothelial cell mitogen extracted from malignant tumors, may be a key mediator in tumor growth. They observed that in isolated perfused organs and heterologous tumor transplantation experiments, tumors failed to grow further when neovascularization was blocked. This led to the hypothesis that angiogenesis is essential for malignant tumor growth. The experiments were conducted on male New Zealand white rabbits using Brown-Pearce rabbit epithelioma tumors. Tumors were implanted either directly on the iris or in the avascular anterior chamber. The growth patterns of these tumors were monitored over time, revealing three distinct phases: prevascular, vascular, and late growth. Prevascular tumors grew slowly and remained small, while vascular tumors rapidly expanded and filled the anterior chamber. Avascular tumors, which did not become vascularized, remained dormant and did not grow beyond a small size. The study found that the onset of vascularization coincided with a sharp increase in tumor volume, suggesting that angiogenesis is necessary for exponential growth. Avascular tumors contained viable and mitotically active cells but failed to expand further. When reimplanted on the iris, avascular tumors vascularized and grew rapidly. The authors conclude that preventing neovascularization can arrest the growth of solid tumors at a small size, indicating that angiogenesis is a critical factor in malignant growth. They suggest that blocking tumor-induced angiogenesis could be an effective strategy for controlling neoplastic growth.This study investigates the relationship between neovascularization and the growth of solid tumors. The authors propose that tumor angiogenesis factor (TAF), an endothelial cell mitogen extracted from malignant tumors, may be a key mediator in tumor growth. They observed that in isolated perfused organs and heterologous tumor transplantation experiments, tumors failed to grow further when neovascularization was blocked. This led to the hypothesis that angiogenesis is essential for malignant tumor growth. The experiments were conducted on male New Zealand white rabbits using Brown-Pearce rabbit epithelioma tumors. Tumors were implanted either directly on the iris or in the avascular anterior chamber. The growth patterns of these tumors were monitored over time, revealing three distinct phases: prevascular, vascular, and late growth. Prevascular tumors grew slowly and remained small, while vascular tumors rapidly expanded and filled the anterior chamber. Avascular tumors, which did not become vascularized, remained dormant and did not grow beyond a small size. The study found that the onset of vascularization coincided with a sharp increase in tumor volume, suggesting that angiogenesis is necessary for exponential growth. Avascular tumors contained viable and mitotically active cells but failed to expand further. When reimplanted on the iris, avascular tumors vascularized and grew rapidly. The authors conclude that preventing neovascularization can arrest the growth of solid tumors at a small size, indicating that angiogenesis is a critical factor in malignant growth. They suggest that blocking tumor-induced angiogenesis could be an effective strategy for controlling neoplastic growth.
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